Title Information
Title
Characterization and suppression of SOD1-mediated ALS phenotype in Drosophila melanogaster knock-in model
Abstract
Amyotrophic Lateral Sclerosis (ALS) is the most common adult-onset neurodegenerative disorder, and is characterized by progressive motor neuron loss that results in muscle weakness, paralysis and eventually death. The molecular mechanisms underlying ALS remain largely unknown, in part, because most animal models of ALS fail to accurately mirror the disease. Whereas many labs have used transgenic overexpression models to produce an ALS phenotype, the Reenan lab has developed a knock-in genetic model in Drosophila. This model introduces specific mutations with known linkage to ALS in humans into the Drosophila SOD1 gene locus. We observed a variety of disease phenotypes ranging in severity and onset, depending on the mutation introduced. This study seeks to further characterize the phenotypes of the various mutant lines. Imaging analysis of the most severe genotype, G85R/G85R, reveals a withered leg phenotype that may correlate to the muscle atrophy seen in human ALS. Additionally, while previous work has shown that H71Y/H71Y mutants are highly susceptible to the introduction of reactive oxygen species, the mutant lines included in the present study appeared to be only moderately susceptible to oxidative stress. We are currently performing a standard EMS mutagenesis suppressor screen. Notably, we have collected a number of surviving flies that appear healthy. However, further work is necessary to confirm the presence of a suppression mutation. We hope the completion of this screen will provide insight into the molecular mechanisms of this disease.
Name: Personal
Name Part
Boaful, Godwin
Role
Role Term
creator
Name: Personal
Name Part
Bredvik, Kirsten
Role
Role Term
creator
Name: Personal
Name Part
Gaztanaga, Wendy
Role
Role Term
creator
Name: Personal
Name Part
Green, Ryan
Role
Role Term
creator
Name: Personal
Name Part
Hackney, Joshua
Role
Role Term
creator
Name: Personal
Name Part
Navarrete, Karla
Role
Role Term
creator
Name: Personal
Name Part
Palaychuk, Natalie
Role
Role Term
creator
Name: Personal
Name Part
Sabetta, Dina
Role
Role Term
creator
Name: Personal
Name Part
Xia, Jimmy
Role
Role Term
creator
Name: Corporate
Name Part
Howard Hughes Medical Institute
Role
Role Term
research program
Name: Personal
Name Part
Reenan, Robert
Role
Role Term
advisor
affiliation
Brown University. Department of Molecular Biology,Cellular Biology and Biochemistry
Origin Information
Publisher
Brown University
Date Created (encoding="w3cdtf")
2014-08-07
Place
Place Term: Text
Providence
Genre (aat)
posters
Subject (Local)
Topic
ALS
Subject (Local)
Topic
Knock-in model
Subject (Local)
Topic
EMS
Subject (Local)
Topic
Mutagenesis
Identifier: DOI
10.26300/ya40-p918
Type of Resource
text