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.

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.