iMAD approach to host-pathogen interaction detection. Recent report.

These authors report a strategy for simultaneous genetic manipulation of the host cell model (Drosophila cells) and pathogen genes (Legionella pneumophila) to identify interactions.

O'Connor TJ, Boyd D, Dorer MS, Isberg RR. Aggravating genetic interactions allow a solution to redundancy in a bacterial pathogen. Science. 2012 Dec 14;338(6113):1440-4. doi: 10.1126/science.1229556. PubMed PMID: 23239729.

"When An Arm is Really a Leg": Disease-related piece by fly genetics-trained science writer R. Lewis

When An Arm is Really a Leg

Lowering A-beta. Recent report.

These authors report a study in flies that led to identification of a conserved protein that is a potential therapeutic target for neurodegenerative disease.

Page RM, Münch A, Horn T, Kuhn PH, Colombo A, Reiner O, Boutros M, Steiner H,
Lichtenthaler SF, Haass C. Loss of PAFAH1B2 Reduces Amyloid-β Generation by Promoting the Degradation of Amyloid Precursor Protein C-Terminal Fragments. J Neurosci. 2012 Dec 12;32(50):18204-18214. PubMed PMID: 23238734.

Pain and the fly. Recent report.

Neely GG, Rao S, Costigan M, Mair N, Racz I, Milinkeviciute G, Meixner A, Nayanala S, Griffin RS, Belfer I, Dai F, Smith S, Diatchenko L, Marengo S, Haubner BJ, Novatchkova M, Gibson D, Maixner W, Pospisilik JA, Hirsch E, Whishaw IQ, Zimmer A, Gupta V, Sasaki J, Kanaho Y, Sasaki T, Kress M, Woolf CJ, Penninger JM. Construction of a global pain systems network highlights phospholipid signaling as a regulator of heat nociception. PLoS Genet. 2012 Dec;8(12):e1003071. doi: 10.1371/journal.pgen.1003071. PMID: 23236288.

ALS study includes tests in new fly models. Recent report.

This study includes report of findings with "a series of transgenic [Drosophila] lines that expressed human WT and mutant EWSR1" developed for the study.

Couthouis J, Hart MP, Erion R, King OD, Diaz Z, Nakaya T, Ibrahim F, Kim HJ, Mojsilovic-Petrovic J, Panossian S, Kim CE, Frackelton EC, Solski JA, Williams KL, Clay-Falcone D, Elman L, McCluskey L, Greene R, Hakonarson H, Kalb RG, Lee VM, Trojanowski JQ, Nicholson GA, Blair IP, Bonini NM, Van Deerlin VM, Mourelatos Z, Shorter J, Gitler AD. Evaluating the role of the FUS/TLS-related gene EWSR1 in amyotrophic lateral sclerosis. Hum Mol Genet. 2012 Jul 1;21(13):2899-911. PMID: 22454397; PMCID: PMC3373238.

Death, aging and the gut. Recent report.

Rera M, Clark RI, Walker DW. Intestinal barrier dysfunction links metabolic and inflammatory markers of aging to death in Drosophila. Proc Natl Acad Sci U S A. 2012 Dec 12. PMID: 23236133.

LRRK2 in the fly model. Recent report.

These authors report findings with potential impact on treatment of Parkinson's Disease. Use the search box (top right-ish of this page) with "LRRK2" to find additional related posts.

Yang D, Li T, Liu Z, Arbez N, Yan J, Moran TH, Ross CA, Smith WW. LRRK2 kinase activity mediates toxic interactions between genetic mutation and oxidative stress in a Drosophila model: suppression by curcumin. Neurobiol Dis. 2012 Sep;47(3):385-92. doi: 10.1016/j.nbd.2012.05.020. PubMed PMID: 22668778.

Fat flies. New Model. Recent report.

Liu J, Li T, Yang D, Ma R, Moran TH, Smith WW. Synphilin-1 alters metabolic homeostasis in a novel Drosophila obesity model. Int J Obes (Lond). 2012 Dec;36(12):1529-36. doi: 10.1038/ijo.2012.111. PMID: 22828940. Corrigendum: Liu J, Li T, Yang D, Ma R, Moran TH, Smith WW. Synphilin-1 alters metabolic homeostasis in a novel Drosophila obesity model. Int J Obes (Lond). 2012 Dec;36(12):1592. doi: 10.1038/ijo.2012.187. PMID: 23229758.

Animal models of Angelman syndrome. Recent review.

Section five of this freely available article covers fly models of Angelman syndrome. 
 Jana NR. Understanding the pathogenesis of Angelman syndrome through animal models. Neural Plast. 2012;2012:710943. doi: 10.1155/2012/710943. Review. PubMed PMID: 22830052; PubMed Central PMCID: PMC3399338.

Fumble helps researchers score. Recent review.

This review mentions how research with a fly fumble disease model contributed to the development of potential therapeutic treatments reportedly slated for clinical trial in 2012. Pantothenate kinase-associated neurodegeneration is a type of NBIA.

Hartig MB, Prokisch H, Meitinger T, Klopstock T. Pantothenate kinase-associated neurodegeneration. Curr Drug Targets. 2012 Aug;13(9):1182-9. Review. PMID: 22515741.

"Spiteful behaviour," opportunistic infections & fly model. Recent report.

Lutter EI, Purighalla S, Duong J, Storey DG. Lethality and cooperation of Pseudomonas aeruginosa quorum-sensing mutants in Drosophila melanogaster infection models. Microbiology. 2012 Aug;158(Pt 8):2125-32. doi:10.1099/mic.0.054999-0. PubMed PMID: 22628480.

Check out this YouTube video on P.a. (aimed at a non-expert audience).

Tau oligomers and disease. Recent review.

This recent review includes information from fly and mammalian models.
Cowan CM, Quraishe S, Mudher A. What is the pathological significance of tau oligomers? Biochem Soc Trans. 2012 Aug;40(4):693-7. doi: 10.1042/BST20120135. PMID: 22817718.

Fly polarity genes and cancer. Recent review.

Elsum I, Yates L, Humbert PO, Richardson HE. The Scribble-Dlg-Lgl polarity module in development and cancer: from flies to man. Essays Biochem. 2012;53:141-68. doi: 10.1042/bse0530141. Review. PubMed PMID: 22928514.

Mitchondria, Parkinsons and flies. Recent review.

Koh H, Chung J. PINK1 as a molecular checkpoint in the maintenance of mitochondrial function and integrity. Mol Cells. 2012 Jul;34(1):7-13. doi: 10.1007/s10059-012-0100-8. Review. PubMed PMID: 22610403.

Tumor progression. Recent report.

These authors use Drosophila as a model to look at tumor progression. They state that the results "provide a mechanistic basis for interclonal tumour progression driven by mitochondrial dysfunction and oncogenic Ras."

Ohsawa S, Sato Y, Enomoto M, Nakamura M, Betsumiya A, Igaki T. Mitochondrial defect drives non-autonomous tumour progression through Hippo signalling in Drosophila. Nature. 2012 Oct 25;490(7421):547-51. doi: 10.1038/nature11452. PubMed PMID: 23023132.

New fly models for ALS. Recent report.

These authors report "new Drosophila transgenic models expressing a full-length wild-type isoform of human FUS protein" and related findings.

Miguel L, Avequin T, Delarue M, Feuillette S, Frébourg T, Campion D, Lecourtois M. Accumulation of insoluble forms of FUS protein correlates with toxicity in Drosophila. Neurobiol Aging. 2012 May;33(5):1008.e1-15. doi:10.1016/j.neurobiolaging.2011.10.008. PubMed PMID: 22118902.

The aging heart. Recent review.

Kaushik G, Zambon AC, Fuhrmann A, Bernstein SI, Bodmer R, Engler AJ, Cammarato A. Measuring passive myocardial stiffness in Drosophila melanogaster to investigate diastolic dysfunction. J Cell Mol Med. 2012 Aug;16(8):1656-62. doi: 10.1111/j.1582-4934.2011.01517.x. Review. PubMed PMID: 22225769; PubMed Central PMCID: PMC3326184.

Here's one of a few views of the fly beating heard on YouTube.

Fly cancer model used as in vivo test. Recent report.

The authors of this open access study describe using a "validated Drosophila cancer model" to test potential radiosensitizing compounds.

Fu S, Yang Y, Tirtha D, Yen Y, Zhou BS, Zhou MM, Ohlmeyer M, Ko EC, Cagan R, Rosenstein BS, Chen SH, Kao J. γ-H2AX kinetics as a novel approach to high content screening for small molecule radiosensitizers. PLoS One. 2012;7(6):e38465. doi: 10.1371/journal.pone.0038465. PMID: 22768044; PubMed Central PMCID: PMC3387170.

Potassium channels and alcohol sensitivity. Recent report.

This paper reports investigation into nervous systems functions of the single Drosophila KCNQ-type voltage-gated potassium channel, KCNQ.

Cavaliere S, Gillespie JM, Hodge JJ. KCNQ Channels Show Conserved Ethanol Block and Function in Ethanol Behaviour. PLoS One. 2012;7(11):e50279. doi: 10.1371/journal.pone.0050279. PubMed PMID: 23209695.

Fly stocks used in the study include a Transgenic RNAi Project (TRiP) fly stock targeting KCNQ that is available from the BDSC.

Screenshot of DIOPT-DIST results with fly KCNQ. Click to enlarge.

In the discussion, the authors write that "it is possible that KCNQ might be a candidate gene to predict susceptibility to alcoholism ..." and "... KCNQ openers may offer a potential new approach to treatment of alcohol- and other drug-misuse disorders."

Human KCNQ genes have previously been associated with epilepsy and seizure disorders, including benign familial neonatal seizures.

Understanding VAPB/vap-33. Recent report.

The authors report investigation into the fly ortholog of VAPB, a human gene that has been linked to ALS, including interaction of the fly VAPB, Vap-33, with Dscam.

Yang Z, Huh SU, Drennan JM, Kathuria H, Martinez JS, Tsuda H, Hall MC, Clemens JC. Drosophila vap-33 is required for axonal localization of dscam isoforms. J Neurosci. 2012 Nov 28;32(48):17241-50. doi: 10.1523/JNEUROSCI.2834-12.2012. PubMed PMID: 23197716.

New fly model of hereditary spastic paraplegia. Recent report.

These authors describe a new fly model of HSP. View other posts on HSP here.

Füger P, Sreekumar V, Schüle R, Kern JV, Stanchev DT, Schneider CD, Karle KN, Daub KJ, Siegert VK, Flötenmeyer M, Schwarz H, Schöls L, Rasse TM. Spastic Paraplegia Mutation N256S in the Neuronal Microtubule Motor KIF5A Disrupts Axonal Transport in a Drosophila HSP Model. PLoS Genet. 2012 Nov;8(11):e1003066. doi:10.1371/journal.pgen.1003066. PubMed PMID: 23209432.

Huntington's Disease gene follow-up in the fly. Recent report.

This open access report includes follow-up of mammalian RNAi screen hits in a fly model of Huntington's disease.

Miller JP, Yates BE, Al-Ramahi I, Berman AE, Sanhueza M, Kim E, de Haro M, Degiacomo F, Torcassi C, Holcomb J, Gafni J, Mooney SD, Botas J, Ellerby LM, Hughes RE. A Genome-Scale RNA-Interference Screen Identifies RRAS Signaling as a Pathologic Feature of Huntington's Disease. PLoS Genet. 2012 Nov;8(11):e1003042. doi: 10.1371/journal.pgen.1003042. PubMed PMID: 23209424.

Melioidosis. Virulence in the fly established. Recent report.

This open source paper describes temperature-dependent virulence of the causative agent of melioidosis in the fly. The authors state that the infectious disease melioidosis is problematic in Southeast Asia and Northern Australia.

Pilátová M, Dionne MS. Burkholderia thailandensis Is Virulent in Drosophila melanogaster. PLoS One. 2012;7(11):e49745. doi: 10.1371/journal.pone.0049745.PubMed PMID: 23209596.

Guilt by association? Using the FlyAtlas 2 "Profile" feature. Recent report and database update.

This recent report describes updates to the FlyAtlas database of gene expression, including the new web interface FlyAtlas 2.

Robinson SW, Herzyk P, Dow JA, Leader DP. FlyAtlas: database of gene expression in the tissues of Drosophila melanogaster. Nucleic Acids Res. 2012 Nov 29. PubMed PMID: 23203866.

Example results from the FlyAtlas 2 "Profile" Search Tool

The new "Profile" feature might help researchers develop new hypotheses regarding gene function based on the functions of genes with similar expression profiles. To create an example, I picked more or less at random from past posts. I chose the gene Prestin, which is related to kidney stones or nephrolithiasis (view the original post here). A single gene match comes up in this case, CG42365, a gene with unknown function that does not appear to have been evolutionarily conserved. I have searched with a handful of gene names. For most genes I searched, the results came back with between ten and a hundred or so genes with similar profiles to that of my entry gene. If you are trying to understand a human disease gene ortholog, searching at FlyAtlas Profiles might be one of many searches that could help in study design and interpretation.

Complex Hereditary Spastic Paraplegia. Supporting evidence in fly. Recent report.

These authors state in the abstract that "An essential role for DDHD2 in the human CNS, and perhaps more specifically in synaptic functioning, is supported by a reduced number of active zones at synaptic terminals in Ddhd-knockdown Drosophila models."

Schuurs-Hoeijmakers JH, Geraghty MT, Kamsteeg EJ, Ben-Salem S, de Bot ST,
Nijhof B, van de Vondervoort II, van der Graaf M, Nobau AC, Otte-Höller I,
Vermeer S, Smith AC, Humphreys P, Schwartzentruber J; FORGE Canada Consortium,
Ali BR, Al-Yahyaee SA, Tariq S, Pramathan T, Bayoumi R, Kremer HP, van de
Warrenburg BP, van den Akker WM, Gilissen C, Veltman JA, Janssen IM, Vulto-van
Silfhout AT, van der Velde-Visser S, Lefeber DJ, Diekstra A, Erasmus CE,
Willemsen MA, Vissers LE, Lammens M, van Bokhoven H, Brunner HG, Wevers RA,
Schenck A, Al-Gazali L, de Vries BB, de Brouwer AP. Mutations in DDHD2, Encoding
an Intracellular Phospholipase A(1), Cause a Recessive Form of Complex Hereditary
Spastic Paraplegia. Am J Hum Genet. 2012 Nov 20. doi:pii: S0002-9297(12)00576-9.
10.1016/j.ajhg.2012.10.017. PubMed PMID: 23176823.

You can view associated human diseases and read about hereditary spastic paraplegias at NCBI's Gene Reviews.

CG17119, the fly, cystinosis, and the future.

CG17119 is a high-confidence putative ortholog of the human gene CTNS, which has been implicated in cystinosis. Results from the DIOPT-DIST are shown below. Phenotypic data in FlyBase, as of this posting, is summarized "No phenotypic data is available."

Fly stocks designed for RNAi knockdown of CG17119 are available from BDSC (TRiP lines) and VDRC. This is just one example of a fly ortholog of a human disease gene. Will it be you who puts the tools in hand to use to study this disease, or another, using the fly?

Click to enlarge or visit www.flyrnai.org/diopt-dist to replicate the search.

Planar Cell Polarity and Kidney Development. Recent review.

This review provides a background on the role of planar cell polarity (PCP), a topic well studied in Drosophila, in the mammalian kidney. The material reviewed is primarily relevant to kidney development but also has relevance to polycystic kidney disease, etc.

Carroll TJ, Yu J. The kidney and planar cell polarity. Curr Top Dev Biol. 2012;101:185-212. doi: 10.1016/B978-0-12-394592-1.00011-9. PubMed PMID: 23140630.

Using fly cells to study the causitive agent for Legionnaires' disease. Recent methods report.

De Jesús DA, O'Connor TJ, Isberg RR. Analysis of Legionella Infection Using RNAi in Drosophila Cells. Methods Mol Biol. 2013;954:251-64. doi: 10.1007/978-1-62703-161-5_15. PubMed PMID: 23150401.

Poly-Q large-scale screen. Recent report.

Voßfeldt H, Butzlaff M, Prüßing K, Ní Chárthaigh RA, Karsten P, Lankes A, Hamm S, Simons M, Adryan B, Schulz JB, Voigt A. Large-scale screen for modifiers of ataxin-3-derived polyglutamine-induced toxicity in Drosophila. PLoS One. 2012;7(11):e47452. doi: 10.1371/journal.pone.0047452. PubMed PMID: 23139745; PubMed Central PMCID: PMC3489908.

Six restless legs. New fly model. Breaking report.

These authors describe a "reverse genetic analysis of a ... poorly understood gene ... and the development of an RLS animal model that closely recapitulates all disease phenotypes." 

An alignment of human BTBD9 and fly CG1826 (a.k.a BTBD9) from DIOPT is shown on the right. Click the image to enlarge.

Freeman A, Pranski E, Miller RD, Radmard S, Bernhard D, Jinnah HA, Betarbet R, Rye DB, Sanyal S. Sleep fragmentation and motor restlessness in a Drosophila model of Restless Legs Syndrome. Curr Biol. 2012 Jun 19;22(12):1142-8. doi:10.1016/j.cub.2012.04.027. PubMed PMID: 22658601; PubMed Central PMCID: PMC3381864.

Shaw PJ, Duntley SP. Neurological disorders: towards a mechanistic understanding of restless legs syndrome. Curr Biol. 2012 Jun 19;22(12):R485-6. doi: 10.1016/j.cub.2012.05.004. PubMed PMID: 22720681.

Read about RSL at PubMed Health.
The RSL Foundation posts RSL Research News.
Genome-wide association study (GWAS) reports include this one in the open access journal PLoS Genetics.

New fly model of Alzheimer's Disease. Breaking report.

Huang JK, Ma PL, Ji SY, Zhao XL, Tan JX, Sun XJ, Huang FD. Age-dependent alterations in the presynaptic active zone in a Drosophila model of Alzheimer's Disease. Neurobiol Dis. 2012 Nov 10. doi:pii: S0969-9961(12)00369-5. 10.1016/j.nbd.2012.11.006. PubMed PMID: 23149068.

BMP signaling, pediatric leukemia and flies. Recent report.

From the abstract:  "Expression of CBFA2T3-GLIS2 in Drosophila and murine hematopoietic cells induced bone morphogenic protein (BMP) signaling and resulted in a marked increase in the self-renewal capacity of hematopoietic progenitors."

Gruber TA, Larson Gedman A, Zhang J, Koss CS, Marada S, Ta HQ, Chen SC, Su X, Ogden SK, Dang J, Wu G, Gupta V, Andersson AK, Pounds S, Shi L, Easton J, Barbato MI, Mulder HL, Manne J, Wang J, Rusch M, Ranade S, Ganti R, Parker M, Ma J, Radtke I, Ding L, Cazzaniga G, Biondi A, Kornblau SM, Ravandi F, Kantarjian H, Nimer SD, Döhner K, Döhner H, Ley TJ, Ballerini P, Shurtleff S, Tomizawa D, Adachi S, Hayashi Y, Tawa A, Shih LY, Liang DC, Rubnitz JE, Pui CH, Mardis ER, Wilson RK, Downing JR. An Inv(16)(p13.3q24.3)-Encoded CBFA2T3-GLIS2 Fusion Protein Defines an Aggressive Subtype of Pediatric Acute Megakaryoblastic Leukemia. Cancer Cell. 2012 Nov 13;22(5):683-97. doi: 10.1016/j.ccr.2012.10.007. PubMed PMID: 23153540.

Flies and alcoholism. Recent book chapter.

Scholz H, Mustard JA. Invertebrate models of alcoholism. Curr Top Behav Neurosci. 2013;13:433-57. doi: 10.1007/7854_2011_128. Review. PubMed PMID: 21472534.

Cancer, FAK and flies. Recent report.

Weisman NY, Golubovsky MD. Cell contact/adhesion proteins Lgl and DFak56: tumorigenic and whole-organism vital effects studied in Drosophila. Anticancer Agents Med Chem. 2011 Sep;11(7):650-7. PubMed PMID: 21707508.

Poly-Q neurodegeneration, p53, nucleoli and flies. Recent report.

This report describes use of Drosophila and mammalian systems to uncover links between PolyQ disease and nucleolar stress.

Tsoi H, Lau TC, Tsang SY, Lau KF, Chan HY. CAG expansion induces nucleolar stress in polyglutamine diseases. Proc Natl Acad Sci U S A. 2012 Aug 14;109(33):13428-33. doi: 10.1073/pnas.1204089109. PubMed PMID: 22847428; PubMed Central PMCID: PMC3421186.

Flies and the plague bacterium. Breaking report.

Paquette N, Conlon J, Sweet C, Rus F, Wilson L, Pereira A, Rosadini CV, Goutagny N, Weber AN, Lane WS, Shaffer SA, Maniatis S, Fitzgerald KA, Stuart L, Silverman N. Serine/threonine acetylation of TGFβ-activated kinase (TAK1) by Yersinia pestis YopJ inhibits innate immune signaling. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12710-5. doi: 10.1073/pnas.1008203109. PubMed PMID: 22802624; PubMed Central PMCID: PMC3411953.

BEACH and flies. Recent report.

This study includes a comparison of phenotypes rescued by mouse and fly Neurobeachin transcripts (fly rugose). The results have implications in understanding BEACH, or beige and human Chediak-Higashi syndrome.

Volders K, Scholz S, Slabbaert JR, Nagel AC, Verstreken P, Creemers JW, Callaerts P, Schwärzel M. Drosophila rugose Is a Functional Homolog of Mammalian Neurobeachin and Affects Synaptic Architecture, Brain Morphology, and Associative Learning. J Neurosci. 2012 Oct 24;32(43):15193-204. doi:10.1523/JNEUROSCI.6424-11.2012. PubMed PMID: 23100440.

Detailed analysis of Drosophila p53. Fly model assessment. Recent report.

This paper describes a molecular characterization of the Drosophila ortholog of human TP53 (p53), a gene commonly associated with cancer. The authors report that fly and human p53 proteins "generally showed a similar energetic and functional response to cancer associated mutations."

Herzog G, Joerger AC, Shmueli MD, Fersht AR, Gazit E, Segal D. Evaluating Drosophila p53 as a model system for studying cancer mutations. J Biol Chem. 2012 Nov 7. PubMed PMID: 23135266.

Fly used to test disease-associated alleles. IMAGe syndrome. Recent report.

In this study, the authors expressed disease-associated mutations in CDKN1C in the fly eye. They report that expression of disease-associated forms but not wild-type caused eye growth defects.

Arboleda VA, Lee H, Parnaik R, Fleming A, Banerjee A, Ferraz-de-Souza B, Délot EC, Rodriguez-Fernandez IA, Braslavsky D, Bergadá I, Dell'Angelica EC, Nelson SF, Martinez-Agosto JA, Achermann JC, Vilain E. Mutations in the PCNA-binding domain of CDKN1C cause IMAGe syndrome. Nat Genet. 2012 May 27;44(7):788-92. doi:10.1038/ng.2275. PubMed PMID: 22634751; PubMed Central PMCID: PMC3386373.

Myotonic Dystrophy Type I. Recent report.

Llamusi B, Bargiela A, Fernandez-Costa JM, Garcia-Lopez A, Klima R, Feiguin F, Artero R. Muscleblind, BSF and TBPH are mislocalized in the muscle sarcomere of a Drosophila myotonic dystrophy model. Dis Model Mech. 2012 Nov 1. PubMed PMID: 23118342.

Flies & Depression.

I did a search today at DIOPT-DIST with "major depressive disorder" (exact match). A long list of human genes identified through genome-wide association study (GWAS) or listed at Online Mendelian Inheritance in Man (OMIM) pop up in the search results. 

Below are genes with high-confidence DIOPT scores as of Nov. 2, 2012 (I'm noting the date because after future updates, the numbers and scores might change). I've opted to show here only the genes with DIOPT scores of seven or better--repeat the search with similar or looser criteria to find many additional putative orthologs of genes linked by GWAS or OMIM to depression. 

Of course it would be next to impossible to identify a "depressed" fly--a term that may not even be relevant to flies. But flies are not just useful to study diseases that can be recapitulated in comparable tissues, organs etc. and displaying phenotypes comparable to the human disease. Flies also useful to dissect interconnected genetic networks and signaling systems, which can be conserved in structure even when they're not regulating the same end outcomes.

FlyBaseID	Fly Symbol	Human GeneID	Human Symbol
FBgn0037094	CG7611	80232	WDR26
FBgn0037382	Hpr1	9984	THOC1
FBgn0033757	muskelin	4289	MKLN1
FBgn0000163	baz	56288	PARD3
FBgn0040777	CG14767	9741	LAPTM4A
FBgn0039169	CG5669	6671	SP4
FBgn0243513	cnir	29097	CNIH4
FBgn0001075	ft	79633	FAT4
FBgn0005671	Vha55	526	ATP6V1B2
FBgn0001991	Ca-alpha1D	775	CACNA1C
FBgn0030778	CG4678	1368	CPM
FBgn0010315	CycD	894	CCND2
FBgn0001104	G-ialpha65A	2773	GNAI3
FBgn0016983	smid	4931	NVL
FBgn0260964	Vmat	6570	SLC18A1

Larval stage fly model of Alzheimer's Disease. Recent report.

Sinadinos C, Quraishe S, Sealey M, Samson PB, Mudher A, Wyttenbach A. Low Endogenous and Chemical Induced Heat Shock Protein Induction in a 0N3Rtau-Expressing Drosophila Larval Model of Alzheimer's Disease. J Alzheimers Dis. 2012 Oct 31. PubMed PMID: 23114515.

Knockdown of SMN in fly neurons and muscles. Recent report.

Loss of SMN1 activity leads to Spinal Muscular Atrophy (SMA). In this study, the fly ortholog of SMN1 was knocked down by RNAi in neurons and muscles.

Timmerman C, Sanyal S. Behavioral and electrophysiological outcomes of tissue-specific Smn knockdown in Drosophila melanogaster. Brain Res. 2012 Oct 25. doi:pii: S0006-8993(12)01692-7. 10.1016/j.brainres.2012.10.035. PubMed PMID: 23103409.

AMP Kinase & Parkinsons. Fly model in action. Recent report.

Ng CH, Guan MS, Koh C, Ouyang X, Yu F, Tan EK, O'Neill SP, Zhang X, Chung J, Lim KL. AMP Kinase Activation Mitigates Dopaminergic Dysfunction and Mitochondrial Abnormalities in Drosophila Models of Parkinson's Disease. J Neurosci. 2012 Oct 10;32(41):14311-14317. PubMed PMID: 23055502.

Bugs & Guts. Recent Report.

In conversation, biologists often use "bugs" to refer to bacteria. This open access report uses the fly as a model to explore the relationship between gastric cancer and infection with the 'bug' Helicobacter pylori, which the authors note is a major risk factor for gastric cancer.

Wandler AM, Guillemin K. Transgenic Expression of the Helicobacter pylori Virulence Factor CagA Promotes Apoptosis or Tumorigenesis through JNK Activation in Drosophila. PLoS Pathog. 2012 Oct;8(10):e1002939. doi:10.1371/journal.ppat.1002939. PubMed PMID: 23093933.

Genetic link related to Parkinson's identified in flies is not reproduced in mammals. Recent report.

Trancikova A, Mamais A, Webber PJ, Stafa K, Tsika E, Glauser L, West AB, Bandopadhyay R, Moore DJ. Phosphorylation of 4E-BP1 in the Mammalian Brain Is Not Altered by LRRK2 Expression or Pathogenic Mutations. PLoS One. 2012;7(10):e47784. doi: 10.1371/journal.pone.0047784. PubMed PMID: 23082216.

Using the fly to study Epstein Barr virus replication. Recent report

In this open access paper, the authors report introducing the Epstein Barr virus gene BRLF1 into flies using a fly eye-specific driver of expression, then identifying host genes that interact with BRLF1.

Adamson A, LaJeunesse D. A study of Epstein-Barr virus BRLF1 activity in a Drosophila model system. ScientificWorldJournal. 2012;2012:347597. doi:10.1100/2012/347597. PubMed PMID: 22629134; PubMed Central PMCID: PMC3353302.

Huntington's Disease. Fly model in action. Recent report.

These authors report a study in which they supplement studies in mammalian models with an assay in "eye degeneration of eye-specific mtHtt (Q127) expressing flies."

Lee J, Hong YK, Jeon GS, Hwang YJ, Kim KY, Seong KH, Jung MK, Picketts DJ, Kowall NW, Cho KS, Ryu H. ATRX induction by mutant huntingtin via Cdx2 modulates heterochromatin condensation and pathology in Huntington's disease. Cell Death Differ. 2012 Jul;19(7):1109-16. doi: 10.1038/cdd.2011.196. PubMed PMID: 22240898; PubMed Central PMCID: PMC3374076.

Similar fly stocks in which expanded repeat forms of human HTT are expressed in the eye or via an inducible promoter are available from the BDSC.

Host-pathogen interactions in model systems. Recent review.

This recent review discusses what's known and open questions regarding host-pathogen interactions as studied in model systems, specifically with biofilms in mind.

Edwards S, Kjellerup BV. Exploring the applications of invertebrate host-pathogen models for in vivo biofilm infections. FEMS Immunol Med Microbiol. 2012 Jul;65(2):205-14. doi: 10.1111/j.1574-695X.2012.00975.x. Review. PubMed PMID: 22533965.

Among other things, the review includes a discussion of a fly-based approach to sub-categorizing bacteria isolated from infections in cystic fibrosis patients.

Sibley CD, Duan K, Fischer C, Parkins MD, Storey DG, Rabin HR, Surette MG. Discerning the complexity of community interactions using a Drosophila model of polymicrobial infections. PLoS Pathog. 2008 Oct;4(10):e1000184. Epub 2008 Oct 24. PubMed PMID: 18949036; PubMed Central PMCID: PMC2566602.

Fly models of neurodevelopmental diseases. Recent review.

This review includes a table of fly models for Angelman Syndrome, Coffin-Lowry Syndrome, Fragile X Syndrome, Neurofibromatosis Type 1, and Periventricular Nodular Heterotropia.

Okray Z, Hassan BA. Genetic approaches in Drosophila for the Study Neurodevelopmental Disorders. Neuropharmacology. 2012 Oct 12. pii:S0028-3908(12)00479-0. doi: 10.1016/j.neuropharm.2012.09.007. PubMed PMID: 23067575.

New fly model of genetic epilepsy with febrile seizures plus. Recent report.

In this study, researchers introduce a human disease-associated mutation into the fly ortholog of SCN1A, para.

Sun L, Gilligan J, Staber C, Schutte RJ, Nguyen V, O'Dowd DK, Reenan R. A knock-in model of human epilepsy in Drosophila reveals a novel cellular mechanism associated with heat-induced seizure. J Neurosci. 2012 Oct 10;32(41):14145-55. doi: 10.1523/JNEUROSCI.2932-12.2012. PubMed PMID: 23055484.

Paraquat, Polyphenols & Parkinsonism. Recent Report.

Bonilla-Ramirez L, Jimenez-Del-Rio M, Velez-Pardo C. Low doses of paraquat and polyphenols prolong life span and locomotor activity in knock-down parkin Drosophila melanogaster exposed to oxidative stress stimuli: Implication in autosomal recessive juvenile Parkinsonism. Gene. 2012 Oct 6. pii: S0378-1119(12)01229-2. doi: 10.1016/j.gene.2012.09.120. PubMed PMID: 23046578.

Inflammatory bowel disease and the fly. Recent review.

This review introduces the fly gut system, summarizes major pathways invoked in gut-microbe responses and talks about gut homeostasis. The results and approaches discussed might impact our understanding of human diseases of the digestive system, including inflammatory bowel disease.

Charroux B, Royet J. Gut-microbiota interactions in non-mammals: what can we learn from Drosophila? Semin Immunol. 2012 Feb;24(1):17-24. Epub 2012 Jan 28. Review. PubMed PMID: 22284578.

Fly model of SMA. SMN in Neural Network Activity. Recent Report.

Imlach WL, Beck ES, Choi BJ, Lotti F, Pellizzoni L, McCabe BD. SMN Is Required for Sensory-Motor Circuit Function in Drosophila. Cell. 2012 Oct 12;151(2):427-39. doi: 10.1016/j.cell.2012.09.011. PubMed PMID: 23063130.

Fly model of mitochondrial dysfunction. Relevance to neurodegenerative diseases. Recent report.

Humphrey DM, Parsons RB, Ludlow ZN, Riemensperger T, Esposito G, Verstreken P, Jacobs HT, Birman S, Hirth F. Alternative oxidase rescues mitochondria-mediated dopaminergic cell loss in Drosophila. Hum Mol Genet. 2012 Jun 15;21(12):2698-712. PubMed PMID: 22398207.

Fly genetic study and gastric cancer. Recent report.

These authors describe screening for modifiers of the effects of expression of gastric cancer-associated mutant gene forms in the fly eye. Follow-up included a chick assay of angiogenesis.

Caldeira J, Simões-Correia J, Paredes J, Pinto MT, Sousa S, Corso G, Marrelli D, Roviello F, Pereira PS, Weil D, Oliveira C, Casares F, Seruca R. CPEB1, a novel gene silenced in gastric cancer: a Drosophila approach. Gut. 2012 Aug;61(8):1115-23. PubMed PMID: 22052064.

The candidate they followed up on is the fly orb gene (CPEB1 in humans).

Flies, Smoke and Parkinson's. Recent Report.

Hill-Burns EM, Singh N, Ganguly P, Hamza TH, Montimurro J, Kay DM, Yearout D, Sheehan P, Frodey K, McLear JA, Feany MB, Hanes SD, Wolfgang WJ, Zabetian CP, Factor SA, Payami H. A genetic basis for the variable effect of smoking/nicotine on Parkinson's disease. Pharmacogenomics J. 2012 Oct 2. doi: 10.1038/tpj.2012.38. PubMed PMID: 23032990.

Fly model of muscular dystrophy and cardiomyopathy.

These reports utilize flies mutant for sarcoglycan (Sgcd), which the authors describe as a fly model of muscular dystrophy and cardiomyopathy. Fly Sgcd is related to human SGCD. 

Both papers are freely available.

Allikian MJ, Bhabha G, Dospoy P, Heydemann A, Ryder P, Earley JU, Wolf MJ, Rockman HA, McNally EM. Reduced life span with heart and muscle dysfunction in Drosophila sarcoglycan mutants. Hum Mol Genet. 2007 Dec 1;16(23):2933-43. PubMed PMID: 17855453.

Goldstein JA, Kelly SM, LoPresti PP, Heydemann A, Earley JU, Ferguson EL, Wolf MJ, McNally EM. SMAD signaling drives heart and muscle dysfunction in a Drosophila model of muscular dystrophy. Hum Mol Genet. 2011 Mar 1;20(5):894-904. PubMed PMID: 21138941; PubMed Central PMCID: PMC3033181.

Here's an alignment of fly Sgcd and human SGCD, as well as other info, from DIOPT (click "view" from DIOPT or the DIOPT score from DIOPT-DIST to reach this page).

Inventory of fly peroxisomal proteins. Links to diseases. Recent report.

This recent paper catalogs fly peroxisomal proteins.

Faust JE, Verma A, Peng C, McNew JA. An Inventory of Peroxisomal Proteins and Pathways in Drosophila melanogaster. Traffic. 2012 Oct;13(10):1378-92. doi: 10.1111/j.1600-0854.2012.01393.x. PubMed PMID: 22758915; PubMed Central PMCID: PMC3443258.

Disruption of peroxisomal-related factors in humans can cause peroxisomal biogenesis disorders such as Zellweger syndrome. Additional relevant disease terms include peroxisomal acyl-CoA oxidase deficiency, rhizomelic chondrodysplasia punctata, Refsum disease, and neonatal adrenoleukodystrophy. You can read about peroxisomal biogenesis disorders at Gene Reviews (includes information about human disease-associated genes).

Evolutionary conservation? The answer appears to be yes. From the paper, "We have identified all of the major vertebrate peroxisomal pathways in Drosophila."

At least these three papers discuss fly models of peroxisomal biogenesis disorders.

Mast FD, Li J, Virk MK, Hughes SC, Simmonds AJ, Rachubinski RA. A Drosophila model for the Zellweger spectrum of peroxisome biogenesis disorders. Dis Model Mech. 2011 Sep-Oct;4(5):659-72. doi: 10.1242/dmm.007419. PubMed PMID: 21669930; PubMed Central PMCID: PMC3180231.

Nakayama M, Sato H, Okuda T, Fujisawa N, Kono N, Arai H, Suzuki E, Umeda M, Ishikawa HO, Matsuno K. Drosophila carrying pex3 or pex16 mutations are models of Zellweger syndrome that reflect its symptoms associated with the absence of peroxisomes. PLoS One. 2011;6(8):e22984. PubMed PMID: 21826223; PubMed Central PMCID: PMC3149631.

Chen H, Liu Z, Huang X. Drosophila models of peroxisomal biogenesis disorder: peroxins are required for spermatogenesis and very-long-chain fatty acid metabolism. Hum Mol Genet. 2010 Feb 1;19(3):494-505. PubMed PMID: 19933170.

Publication searches. Multiple tools.

A search with "Drosophila disease model" calls up different results in Quertle, Google Scholar and PubMed. And the three tools provide different search options. Check it out.

Cancer and the immune response. Recent report.

This recent report looks at the influence of infection in a fly model of cancer (Ras1[V12] model).

Bangi E, Pitsouli C, Rahme LG, Cagan R, Apidianakis Y. Immune response to bacteria induces dissemination of Ras-activated Drosophila hindgut cells. EMBO Rep. 2012 Jun 1;13(6):569-76. doi: 10.1038/embor.2012.44. PubMed PMID: 22498775; PubMed Central PMCID: PMC3367237.

A-beta and zinc transport. Recent report.

This open access paper focuses on the potential role of a zinc transporter in Alzheimer's disease.

Lang M, Wang L, Fan Q, Xiao G, Wang X, Zhong Y, Zhou B. Genetic inhibition of solute-linked carrier 39 family transporter 1 ameliorates aβ pathology in a Drosophila model of Alzheimer's disease. PLoS Genet. 2012;8(4):e1002683. PubMed PMID: 22570624; PubMed Central PMCID: PMC3343105.

They indicate that they use the fly A-beta42 model reported here:  Iijima et al. (2008) Abeta 42 Mutants with Different Aggregation Profiles Induce Distinct Pathologies in Drosophila. PLoS ONE 3: e1703. PubMed ID: 18301778 PubMed Central ID: PMC225077

Click to view a recent post on a chemical inhibitor of A-beta.

SMBA & Poly-Q study. Recent report.

Jochum T, Ritz ME, Schuster C, Funderburk SF, Jehle K, Schmitz K, Brinkmann F, Hirtz M, Moss D, Cato AC. Toxic and non-toxic aggregates from the SBMA and normal forms of androgen receptor have distinct oligomeric structures. Biochim Biophys Acta. 2012 Jun;1822(6):1070-8. PubMed PMID: 22366762.

The authors indicate that they used two existing fly stocks, pUAST-ARQ22 and pUAST-ARQ22dm, and generated two new transgenic stocks, pUAST-ARQ1 and -ARQ65, for the study. These are pathogenic forms of the human androgen receptor protein. See this FlyBase page for more info on human AR transgenic flies. To induce expression of the AR forms, these authors used the OK371-GAL4 driver fly stock.

Circadian rhythms & fragile X. Fly models in action. Recent report.

This open access paper uses what is described as a Drosophila dfmr1 null mutant strain, dFmr1-Del3-21/TM6C, Kr:GFP.

Xu S, Poidevin M, Han E, Bi J, Jin P. Circadian rhythm-dependent alterations of gene expression in Drosophila brain lacking fragile X mental retardation protein. PLoS One. 2012;7(5):e37937. PubMed PMID: 22655085; PubMed Central PMCID: PMC3360013.

See also BDSC's fly stocks page for Fragile X Syndrome.
And a past post on a paper linking the circadian clock to neurodegenerative disease.

New fly model of Inclusion Body Myopathy 3. Recent report.

This study describes a new fly model based on introduction of a human disease-associated missense mutation (E706K) in myosin heavy chain IIa. The mutant form was introduced via P-element transformation and crossed into an Mhc null mutant background.

Wang Y, Melkani GC, Suggs JA, Melkani A, Kronert WA, Cammarato A, Bernstein SI. Expression of the inclusion body myopathy 3 mutation in Drosophila depresses myosin function and stability and recapitulates muscle inclusions and weakness. Mol Biol Cell. 2012 Jun;23(11):2057-65. Epub 2012 Apr 11. PubMed PMID: 22496423; PubMed Central PMCID: PMC3364171.

LRRK2 as a critical regulator of EndophilinA. Parkinson's model in action. Recent report.

From the abstract: "LRRK2-mediated EndoA phosphorylation has profound effects on EndoA-dependent membrane tubulation and membrane association ... and on synaptic vesicle endocytosis at Drosophila neuromuscular junctions in vivo." The authors report use of both loss-of-function and gain-of-function genetic approaches in the study.

Matta S, Van Kolen K, da Cunha R, van den Bogaart G, Mandemakers W, Miskiewicz K, De Bock PJ, Morais VA, Vilain S, Haddad D, Delbroek L, Swerts J, Chávez-Gutiérrez L, Esposito G, Daneels G, Karran E, Holt M, Gevaert K, Moechars DW, De Strooper B, Verstreken P. LRRK2 Controls an EndoA Phosphorylation Cycle in Synaptic Endocytosis. Neuron. 2012 Sep 20;75(6):1008-21. doi: 10.1016/j.neuron.2012.08.022. PubMed PMID: 22998870.

Click to see a post on a loss-of-function fly study of Lrrk2.
Or other posts on Parkinson's Disease.
Or other posts on neurodegeneration diseases of many types.

A-beta inhibitor tested in a fly model of Alzheimer's disease. Recent report.

McKoy AF, Chen J, Schupbach T, Hecht MH. A novel inhibitor of Aβ peptide aggregation: from high throughput screening to efficacy in an animal model for Alzheimer's disease. J Biol Chem. 2012 Sep 19. PubMed PMID: 22992731.

The fly model is described in the methods section as follows "female flies carrying the Aβ42 or Aβ42/E22G transgene under the UAS promoter in a homozygous condition ... crossed with male flies carrying the driver Elav[c155]-Gal4 on their X- chromosome."

Fly model of kidney stones. Recent report.

Hirata T, Cabrero P, Berholtz DS, Bondeson DP, Ritman EL, Thompson JR, Dow JA, Romero MF. In vivo Drosophila genetic model for calcium oxalate nephrolithiasis. Am J Physiol Renal Physiol. 2012 Sep 19. PubMed PMID: 22993075.

Relevant fly gene: Prestin (or dPrestin).
Nephrolithiasis is commonly known as kidney stones.

cAMP & Fragile X syndrome. Recent report.

Kanellopoulos AK, Semelidou O, Kotini AG, Anezaki M, Skoulakis EM. Learning and memory deficits consequent to reduction of the fragile x mental retardation protein result from metabotropic glutamate receptor-mediated inhibition of cAMP signaling in Drosophila. J Neurosci. 2012 Sep 19;32(38):13111-24. PubMed PMID: 22993428.

Chemical screen in fly tumor model. Recent report.

Free access available to this paper on chemical screening in a fly tumor model.

Willoughby LF, Schlosser T, Manning SA, Parisot JP, Street IP, Richardson HE, Humbert PO, Brumby AM. An in vivo large-scale chemical screening platform using Drosophila for anti-cancer drug discovery. Dis Model Mech. 2012 Sep 20. PubMed PMID: 22996645.

Fly wing genetic study helps define epigenetic network involved in cognition. Recent report.

This paper provides a nice example of how genetic studies in the fly can inform the interpretation of human disease-related next generation sequencing (NGS) results. 

Their Supplemental Table 7 lists the fly stocks they used in the study.

Kleefstra T, Kramer JM, Neveling K, Willemsen MH, Koemans TS, Vissers LE, Wissink-Lindhout W, Fenckova M, van den Akker WM, Kasri NN, Nillesen WM, Prescott T, Clark RD, Devriendt K, van Reeuwijk J, de Brouwer AP, Gilissen C, Zhou H, Brunner HG, Veltman JA, Schenck A, van Bokhoven H. Disruption of an EHMT1-associated chromatin-modification module causes intellectual disability. Am J Hum Genet. 2012 Jul 13;91(1):73-82. PubMed PMID: 22726846; PubMed Central PMCID: PMC3397275.

From the paper:

"Drosophila genetic interaction studies with established disease genes thus provide an efficient and, in our opinion, urgently required method of discriminating between rare or even unique benign DNA variants and causative mutations in the NGS era."

Crawling assay useful for assessing neurological disorder fly models. Recent report.

It's not just about your model fly. It's also about how you test it. 

This report describes a quantitative larval crawling assay that reveals impaired crawling in disease models of Alzheimer's disease (AD) and Fragile X syndrome. They also note that their findings with shaggy mutant animals might be relevant to the use of GSK-3 inhibitors in treating AD.

Jakubowski B, Longoria R, Shubeita G. A high throughput and sensitive method correlates neuronal disorder genotypes to Drosophila larvae crawling phenotypes. Fly (Austin). 2012 Sep 19;6(4). PubMed PMID: 22992470.

Plant extract effects on rotenone-induced neurotoxicity. Recent report.

This report describes using Drosophila to test of the potential antioxidant properties of a plant extract.

Girish C, Muralidhara. Propensity of Selaginella delicatula aqueous extract to offset rotenone-induced oxidative dysfunctions and neurotoxicity in Drosophila melanogaster: Implications for Parkinson's disease. Neurotoxicology. 2012 Jun;33(3):444-56. PubMed PMID: 22521218.

As of this posting, the number of PubMed cataloged papers on Selaginella delicatula is small. It's a pteridophyte. Some previous posts point to papers looking at the effects of fruit extracts, methylene blue and L-ascorbic acid on fly neurodegeneration models.

Parkinson's associated LRRK2 ortholog study. Recent report.

This study describes analysis of loss-of-function of the Drosophila ortholog of LRRK2 (dLRRK), as well as analysis of the effects of over-expression of wild-type Drosophila and human LRRK2, and a pathogenic mutant form (hLRRK2-G2019S). The authors point out that LRRK2 is associated with familial and sporadic forms of Parkinson's Disease.

Lee S, Imai Y, Gehrke S, Liu S, Lu B. The synaptic function of LRRK2. Biochem Soc Trans. 2012 Oct 1;40(5):1047-51. PubMed PMID: 22988863.

Fly study links Ellis-van Creveld syndrome genes to Hedgehog pathway. Recent report.

Yang C, Chen W, Chen Y, Jiang J. Smoothened transduces Hedgehog signal by forming a complex with Evc/Evc2. Cell Res. 2012 Sep 18. doi: 10.1038/cr.2012.134. PubMed PMID: 22986504.

Additional ciliopathies for which there are putative fly orthologs of the human disease-associated genes include Ciliary Dykinesia, Joubert Syndrome and Bardet-Biedl Syndrome.

Drosophila as a model for lead toxicity. Recent report.

Hirsch HV, Lnenicka G, Possidente D, Possidente B, Garfinkel MD, Wang L, Lu X, Ruden DM. Drosophila melanogaster as a model for lead neurotoxicology and toxicogenomics research. Front Genet. 2012;3:68. PubMed PMID: 22586431; PubMed Central PMCID: PMC3343274.

The authors point out that parallels between the effects of lead poisoning and disorders such as attention deficit hyperactivity disorder (ADHD) suggest that studying lead neurotoxicology might have impact in additional fields of study.

Cohesinopathies. Recent review.

This review discusses fly and other models of cohesinopathies, which include Cornelia de Lange Syndrome and Roberts Syndrome.

Horsfield JA, Print CG, Mönnich M. Diverse developmental disorders from the one ring: distinct molecular pathways underlie the cohesinopathies. Front Genet. 2012;3:171. PubMed PMID: 22988450.

Among the genes discussed is Nipped-B, the fly ortholog of the human gene associated with Cornelia de Lange Syndrome. Table 1 of the review lists additional genes relevant to cohesinopathies.

Menkes and Wilsons Diseases. Recent report.

Menkes and Wilson diseases are related to copper homeostasis. This study looks at the Drosophila ortholog of the human genes associated with Menkes and Wilson diseases, Drosophila ATP7.

Sellami A, Wegener C, Veenstra JA. Functional significance of the copper transporter ATP7 in peptidergic neurons and endocrine cells in Drosophila melanogaster. FEBS Lett. 2012 Aug 16. PubMed PMID: 22981378.

Fly and mouse models of Alzheimer's Disease. Therapeutics development. Recent report.

Scherzer-Attali R, Farfara D, Cooper I, Levin A, Ben-Romano T, Trudler D, Vientrov M, Shaltiel-Karyo R, Shalev DE, Segev-Amzaleg N, Gazit E, Segal D, Frenkel D. Naphthoquinone-tyrptophan reduces neurotoxic Aβ*56 levels and improves cognition in Alzheimer's disease animal model. Neurobiol Dis. 2012 Jun;46(3):663-72. PubMed PMID: 22449754.

The fly model is described in the paper this way:  "Male flies carrying the driver elav-c155-Gal4 (on their X chromosome) were crossed to females carrying the Aβ1–42 transgene (located on an  autosome) under the UAS promoter in a homozygous condition. This resulted in first generation (F1) female offspring expressing Aβ1–42 in their nervous system. ... Male F1 offspring, which carried the Aβ1–42 transgene but did not express it (because they lacked the Gal4 driver) served as a control."

Resources related Alzheimer's Disease:

Alzheimer Research Forum
BDSC's AD fly stocks page
Past posts on AD

Fly models of neurodegenerative disease. Recent review.

This recent review has an emphasis on forward genetic screens, such as screens for the 'bang sensitive' phenotype or for short-lived flies, or using electroretinograms.

Jaiswal M, Sandoval H, Zhang K, Bayat V, Bellen HJ. Probing Mechanisms that Underlie Human Neurodegenerative Disease in Drosophila. Annu Rev Genet. 2012 Sep 4. PubMed PMID: 22974305.

Fly mauve mutant as model for Chediak-Higashi syndrome. Recent report.

This report describes a new fly model of Chediak-Higashi syndrome (CHS), a disease affecting lysosomes.

Rahman M, Haberman A, Tracy C, Ray S, Kramer H. Drosophila mauve mutants reveal a role of LYST homologs late in the maturation of phagosomes and autophagosomes. Traffic. 2012 Aug 30. doi: 10.1111/tra.12005. PubMed PMID: 22934826.

As of this posting, FlyBase has separate records for mauve (FBgn0014363) and the sequenced region identified as mauve in the paper, CG42863 (FBgn0262110). The CG number or its FlyBase ID pulls up results with a FlyMine search (mauve does not yet match to FlyMine records).

Genes related to fly eye color have contributed to the study of other disease models. See for example this post on a fly glycerol kinase deficiency model.

Looking to get started learning more about CHS? There is summary information about the disease available at GeneReviews.

Drosophila neurodegeneration model and proteomics. Conserved findings. Recent report.

Wishart TM, Rooney TM, Lamont DJ, Wright AK, Morton AJ, Jackson M, Freeman MR, Gillingwater TH. Combining comparative proteomics and molecular genetics uncovers regulators of synaptic and axonal stability and degeneration in vivo. PLoS Genet. 2012 Aug;8(8):e1002936. PubMed PMID: 22952455; PubMed Central PMCID: PMC3431337

From the abstract:  "... An initial screen targeting thirteen degeneration-associated proteins using mutant Drosophila lines revealed six potential regulators of synaptic and axonal degeneration in vivo. Mutations in CALB2, ROCK2, DNAJC5/CSP, and HIBCH partially delayed injury- nduced neurodegeneration. Conversely, mutations in DNAJC6 and ALDHA1 led to spontaneous degeneration of distal axons and synapses. A more detailed genetic analysis ..."

Disease-related ortholog tool improved. DIOPT-DIST with fuzzy search.

The DRSC has just updated the DIOPT-DIST tool to allow for more 'forgiving' searches in the search field, "Or disease full text search."

Before, a search with "Parkinson" might pull up different results than a search with "Parkinson's" or "Parkinsonism" would deliver. Now, all these terms pull up the same list, and even a misspelling like "Parksinson" will get you where you mean to be.

The back end does not have an extensive set of disease synonyms, so the DRSC still suggests trying different synonyms of diseases (or OMIM IDs). But hopefully the fuzzy search will make things a whole lot easier.

Flies on a death spiral. Modeling physiological decline. Recent report.

This recent study describes several assays that can be used to assess physiological and age-related decline in flies.

Shahrestani P, Tran X, Mueller LD. Physiology declines prior to death in Drosophila melanogaster. Biogerontology. 2012 Sep 9. [Epub ahead of print] PubMed PMID: 22960750.

Charcot Marie Tooth Syndrome and Atypical Optic Atrophy. Recent report.

Eschenbacher WH, Song M, Chen Y, Bhandari P, Zhao P, Jowdy CC, Engelhard JT, Dorn GW 2nd. Two rare human mitofusin 2 mutations alter mitochondrial dynamics and induce retinal and cardiac pathology in Drosophila. PLoS One. 2012;7(9):e44296. PubMed PMID: 22957060

See also all posts on CMT.

Fragile-X. Recent report.

Another paper describing use of a fly model of a neurodegenerative disease.

Qurashi A, Liu H, Ray L, Nelson DL, Duan R, Jin P. Chemical screen reveals small molecules suppressing fragile X premutation rCGG repeat-mediated neurodegeneration in Drosophila. Hum Mol Genet. 2012 May 1;21(9):2068-75. PubMed PMID: 22298836; PubMed Central PMCID: PMC3315210.

Related resource:  BDSC's page on fly stocks related to fragile-X syndrome.

AD fly model and mitochondria. Recent report.

Open access paper using a fly model of Alzhemer's Disease.

Iijima-Ando K, Sekiya M, Maruko-Otake A, Ohtake Y, Suzuki E, Lu B, Iijima KM. Loss of Axonal Mitochondria Promotes Tau-Mediated Neurodegeneration and Alzheimer's Disease-Related Tau Phosphorylation Via PAR-1. PLoS Genet. 2012 Aug;8(8):e1002918. PubMed PMID: 22952452.

Progressive External Ophthalmoplegia. Recent report.

This open access paper reports a new in vivo fly model of disease, in this case modeling autosomal dominant progressive external ophthalmoplegia (adPEO).

Sanchez-Martinez A, Calleja M, Peralta S, Matsushima Y, Hernandez-Sierra R, Whitworth AJ, Kaguni LS, Garesse R. Modeling pathogenic mutations of human twinkle in Drosophila suggests an apoptosis role in response to mitochondrial defects. PLoS One. 2012;7(8):e43954. PubMed PMID: 22952820

The fly gene used to model the disease in flies is referred to in the paper as d-mtDNA helicase (d-mtDNA). It has the systematic name CG5924 and the FlyBase ID FBgn0032154.

FlyBase lists 2 TRiP RNAi fly stocks and two additional stocks for CG5924 available from the BDSC, as well as one RNAi fly stock at the VDRC and one transposon insertion strain in the Exilixis collection at HMS. These resources would be useful to study the reduction-of-function phenotypes of the gene, which in this case is different from the disease model, which is based on over-expression.

A related reduction-of-function (RNAi) and over-expression study in fly cells is described in this paper: Matsushima Y, Kaguni LS. Differential phenotypes of active site and human autosomal dominant progressive external ophthalmoplegia mutations in Drosophila mitochondrial DNA helicase expressed in Schneider cells. J Biol Chem. 2007 Mar 30;282(13):9436-44. PubMed PMID: 17272269.

To read more about adPEO and related diseases or disorders, consider starting here:

adPEO attributed to the twinkle gene at OMIM
PEO search results at OMIM (additional related diseases)
POLG-related disorders at Gene Reviews
Mitochondrial diseases overview at Gene Reviews
Related research projects listed at Orphanet
Info on PEO at Genetics Home Reference

Recommended search term for finding more putative orthologs of PEO-related human disease genes at DIOPT-DIST is "ophthalmoplegia" (without quote marks) in the box "Or disease full text search."

Fruit extracts and neurodegeneration. Recent report.

This recent report describes testing the potential therapeutic effects of fruit-derived compounds using a fly model of neurodegenerative disease (a transgenic fly strain expressing human A-beta-42).

Yu Y, Feng XL, Gao H, Xie ZL, Dai Y, Huang XJ, Kurihara H, Ye WC, Zhong Y, Yao XS. Chemical constituents from the fruits of Gardenia jasminoides Ellis. Fitoterapia. 2012 Apr;83(3):563-7. PubMed PMID: 22245087

Models like this in which a disease-associated human gene is expressed in flies are available from the BDSC. Check out BDSC's page on Alzheimers disease fly stocks for example.

Immunity and age-related disease. Recent review.

This open access review discusses fly models related to aging and immunity.

Eleftherianos I, Castillo JC. Molecular mechanisms of aging and immune system regulation in Drosophila. Int J Mol Sci. 2012;13(8):9826-44. PubMed PMID: 22949833

Using Drosophila to study obesity and diabetes. Recent mini-review.

This recent mini-review provides an overview and references for specific models.

Teleman AA, Ratzenböck I, Oldham S. Drosophila: a model for understanding obesity and diabetic complications. Exp Clin Endocrinol Diabetes. 2012 Apr;120(4):184-5. PubMed PMID: 22402943.

Parkinson's Disease, Miro and Mitochondria. Recent Report.

Liu S, Sawada T, Lee S, Yu W, Silverio G, Alapatt P, Millan I, Shen A, Saxton W, Kanao T, Takahashi R, Hattori N, Imai Y, Lu B. Parkinson's disease-associated kinase PINK1 regulates Miro protein level and axonal transport of mitochondria. PLoS Genet. 2012;8(3):e1002537. PubMed PMID: 22396657; PubMed Central PMCID: PMC3291531.

Related resource: BDSC's collection of Parkinson's disease-related fly stocks.
RNAi fly stocks for dMiro are available from the VDRC and TRiP--see FlyBase record for dMiro.

Comparison of the glycobiology of humans and flies. Foundational review.

In this recent review, the authors provide a comparison of human and fly glycobiology and describe the "increasing opportunities to dissect pathologic mechanisms using Drosophila genetics."


Katoh T, Tiemeyer M. The N's and O's of Drosophila glycoprotein glycobiology. Glycoconj J. 2012 Aug 31. PubMed PMID: 22936173

The authors indicate that the proteins and pathways discussed are relevant to a number of diseases, including retinitis pigmentosa, Peters Plus syndrome, and diseases "such as autoimmunity, cancer progression, and congenital heart disease, in which altered mucin type O-glycosylation has been implicated." 

Peters Plus syndrome is also known as Krause–van Schooneveld–Kivlin syndrome and Krause–Kivlin syndrome. It is listed on Orphanet and you can read more about it at GeneReviews.

If someone has the time and inclination to pull out the Drosophila gene names mentioned in the paper, and list them as a comment here, please do so.

Phosphate toxicity and lifespan. Recent review.

This review describes how Drosophila can be used to model dietary phosphate toxicity or hyperphosphatemia, an imbalance that can be associated with chronic kidney disease.

Bergwitz, C. Dietary phosphate modifies lifespan in Drosophila. Nephrol. Dial. Transplant. (2012) 27(9): 3399-3406 . PubMed ID: 22942172

Resource for disease information: GeneReviews.

The NCBI Bookshelf includes GeneReviews, which has detailed information about many human diseases, including information about relevant genes. Another resource to check out if you're looking to dive deep into a particular disease and focus fly research in disease-relevant directions. See links for more.

Drosophila models of deafness. Foundational report.

This paper describes a large-scale effort to further develop Drosophila as a model for study of hearing and hearing-related diseases.

Pingkalai R. Senthilan, David Piepenbrock, Guvanch Ovezmyradov, Björn Nadrowski, Susanne Bechstedt, Stephanie Pauls, Margret Winkler, Wiebke Möbius, Jonathon Howard, Martin C. Göpfert. Drosophila Auditory Organ Genes and Genetic Hearing Defects. Cell 31 August 2012 (Vol. 150, Issue 5, pp. 1042-1054).

The study includes but is not limited to comparative mRNA analysis to identify relevant transcripts; in situ hybridization to visualize transcripts in a relevant organ; and characterization of auditory phenotypes. A Cell 'Preview' article by Lewis & Steel is also available. These authors describe the study by Senthilan et al. as providing "a new resource to aid identification of genes involved in deafness."

GWAS suggests role for KCNJ2 in thyrotoxic periodic paralysis.

This GWAS-identified human gene has a fly ortholog, too? Yes, it seems so.

Cheung CL, Lau KS, Ho AY, Lee KK, Tiu SC, Lau EY, Leung J, Tsang MW, Chan KW, Yeung CY, Woo YC, Cheung EY, Hung VH, Pang HK, Hung CS, Sham PC, Kung AW. Genome-wide association study identifies a susceptibility locus for thyrotoxic periodic paralysis at 17q24.3. Nat Genet. 2012 Aug 5. doi: 10.1038/ng.2367. PubMed PMID: 22863731

The top-scoring Drosophila DIOPT result for human KCNJ2 is Irk2. 
Other related genes include Ir and Irk3.

The Gal4-UAS system could be used to test RNAi knockdown of these genes, as the FlyBase reports (click gene links above) show that RNAi fly stocks from the Transgenic RNAi Project (TRiP) and Vienna Drosophila RNAi Center (VDRC) exist for these genes.

According to Wikipedia, thyrotoxic periodic paralysis is classified under the larger umbrella of channelopathies, which also include alternating hemiplegia of childhood.

GWAS implicates ATP1A3 in alternating hemiplegia of childhood.

A genome-wide association study points to mutations in the human gene ATP1A3 as causative in alternating hemiplegia of childhood (AHC). The authors state that distinct mutations in same gene has been implicated in rapid-onset dystonia-parkinsonism.

Heinzen EL, Swoboda KJ, Hitomi Y, Gurrieri F, Nicole S, et al. De novo mutations in ATP1A3 cause alternating hemiplegia of childhood. Nat Genet. 2012 Jul 29. doi:10.1038/ng.2358. PubMed PMID: 22842232.

The fly ortholog of ATP1A3 appears to be ATPalpha (FBgn0002921) (DIOPT score = 8, indicating that 8 of 9 published ortholog prediction algorithms/tools predict this human-fly gene relationship).

As annotated in FlyBase, researchers have isolated a large number of mutations in ATPalpha and mutant phenotypes include lethality, the 'bang sensitive' phenotype, hypoactivity, paralysis and neurophysiological defects. Presumably these existing fly models could be used to study AHC.

GWAS implicates NMNAT1 in Leber congential amaurosis.

Two reports in the recent issue of Nature Genetics implicate the human gene NMNAT1 in Leber congenital amaurosis, rare inherited eye disease.

Chiang PW, Wang J, Chen Y, Fu Q, Zhong J, Chen Y, Yi X, Wu R, Gan H, Shi Y, Chen Y, Barnett C, Wheaton D, Day M, Sutherland J, Heon E, Weleber RG, Gabriel LA, Cong P, Chuang K, Ye S, Sallum JM, Qi M. Exome sequencing identifies NMNAT1 mutations as a cause of Leber congenital amaurosis. Nat Genet. 2012 Jul 29. doi:10.1038/ng.2370. PubMed PMID: 22842231.

Koenekoop RK, Wang H, Majewski J, Wang X, Lopez I, Ren H, Chen Y, Li Y, Fishman GA, Genead M, Schwartzentruber J, Solanki N, Traboulsi EI, Cheng J, Logan CV, McKibbin M, Hayward BE, Parry DA, Johnson CA, Nageeb M; Finding of Rare Disease Genes (FORGE) Canada Consortium, Poulter JA, Mohamed MD, Jafri H, Rashid Y, Taylor GR, Keser V, Mardon G, Xu H, Inglehearn CF, Fu Q, Toomes C, Chen R. Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration. Nat Genet. 2012 Jul 29. doi: 10.1038/ng.2356. PubMed PMID: 22842230.

The fly ortholog of NMNAT1 is Nmnat (for Nicotinamide mononucleotide adenylyltransferase). As annotated in FlyBase, phenotypes observed for mutations in Drosophila Nmnat include phenotypes associated with the eye.

More info on the human genetics of Leber congential amaurosis is available here.

Signal-mediated growth control and mitochondria. Recent report.

This recent report links mitochondrial fusion and cancer-relevant, signal-mediated growth control by the hippo signal transduction pathway. 

A link to mitochondria sounds familiar? Mitochondrial dynamics were recently linked to neurodegenerative disease as well--see this post.

Nagaraj R, Gururaja-Rao S, Jones KT, Slattery M, Negre N, Braas D, Christofk H, White KP, Mann R, Banerjee U. Control of mitochondrial structure and function by the Yorkie/YAP oncogenic pathway. Genes Dev. 2012 Aug 27. PubMed PMID: 22925885

The hippo signaling pathway has its own Wikipedia page. And as of this posting, it's been nominated but not yet created as a pathway at WikiPathways.

Brain disease and fly models. Foundational review.

This review touches on a number of neurological and neuromuscular degenerative diseases, metabolic disorders, tumors, epilepsy and trauma (injury and regeneration).

Jeibmann & Paulus (2009) Drosophila melanogaster as a model organism of brain diseases. Int J Mol Sci. 2009 Feb;10(2):407-40. PubMed: 19333415; PubMed Central: PMC2660653.

Molecular chaperones and ALS. Recent Report.

This open access paper describes use of a fly model of amyotrophic lateral sclerosis (ALS), which is also known as Lou Gehrig's disease, to link protein aggregation to neurotoxicity.

Gregory JM, Barros TP, Meehan S, Dobson CM, Luheshi LM. The aggregation and neurotoxicity of TDP-43 and its ALS-associated 25 kDa fragment are differentially affected by molecular chaperones in Drosophila. PLoS One. 2012;7(2):e31899. PubMed PMID: 22384095; PubMed Central PMCID: PMC3284513.

Flies used in the study include transgenic animals in which the Gal4-UAS system was used to express HA-tagged TDP-43.

See also the Bloomington Drosophila Stock Center's page on ALS-related fly stocks. 

A search with "amyotrophic lateral sclerosis" (without the quotes) entered into the box "Or disease full text search" at DIOPT-DIST brings up more than 100 results.

This YouTube video (unrelated to the article cited above) shows a comparison of flies mutant for an ALS-related gene ortholog with normal flies in the "climbing assay," a simple assay of motor control.  After a quick tap of the vial, normal flies will reorient themselves and crawl to the top of the vial.

Mitochondria and neurodegeneration. Recent Report.

A breaking report newly implicates mitochondrial dynamics in neurodegenerative disease.

Duboff B, Götz J, Feany MB. Tau Promotes Neurodegeneration via DRP1 Mislocalization In Vivo. Neuron. 2012 Aug 23;75(4):618-32. PubMed PMID: 22920254

Fly model used (from the Materials and Methods): "Our Drosophila model of tauopathy is based on expression of either wild-type or FTDP-17 linked mutant forms of tau in neurons using the UAS/GAL4 bipartite expression system (Brand and Perrimon, 1993) and a panneuronal driver (elav-GAL4). In these studies, we predominantly express human tau carrying the R406W mutation ... To examine mitochondrial morphology in our model, we coexpressed tau with mitochondrially localized GFP (mitoGFP) in neurons of the adult brain."

Update: this review article looks relevant: Itoh K, Nakamura K, Iijima M, Sesaki H. Mitochondrial dynamics in neurodegeneration. Trends Cell Biol. 2013 Feb;23(2):64-71. PMID: 23159640; PMCID: PMC3558617.