Wednesday, November 28, 2012

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.

Tuesday, November 27, 2012

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 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.

Wednesday, November 21, 2012

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.

Tuesday, November 20, 2012

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.

Saturday, November 17, 2012

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.

Friday, November 9, 2012

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.

Thursday, November 8, 2012

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.

Friday, November 2, 2012

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.


Fly Symbol

Human GeneID

Human Symbol





























































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.