Freeman Lab Student Publications

Title

Using Drosophila models of Huntington's disease as a translatable tool

UMMS Affiliation

Department of Neurobiology; Freeman Lab; Graduate School of Biomedical Sciences, Neuroscience Program

Date

5-30-2016

Document Type

Article

Disciplines

Genetics and Genomics | Nervous System Diseases | Neuroscience and Neurobiology

Abstract

The Huntingtin (Htt) protein is essential for a wealth of intracellular signaling cascades and when mutated, causes multifactorial dysregulation of basic cellular processes. Understanding the contribution to each of these intracellular pathways is essential for the elucidation of mechanisms that drive pathophysiology. Using appropriate models of Huntington's disease (HD) is key to finding the molecular mechanisms that contribute to neurodegeneration. While mouse models and cell lines expressing mutant Htt have been instrumental to HD research, there has been a significant contribution to our understating of the disease from studies utilizing Drosophila melanogaster. Flies have an Htt protein, so the endogenous pathways with which it interacts are likely conserved. Transgenic flies engineered to overexpress the human mutant HTT gene display protein aggregation, neurodegeneration, behavioral deficits and a reduced lifespan. The short life span of flies, low cost of maintaining stocks and genetic tools available for in vivo manipulation make them ideal for the discovery of new genes that are involved in HD pathology. It is possible to do rapid genome wide screens for enhancers or suppressors of the mutant Htt-mediated phenotype, expressed in specific tissues or neuronal subtypes. However, there likely remain many yet unknown genes that modify disease progression, which could be found through additional screening approaches using the fly. Importantly, there have been instances where genes discovered in Drosophila have been translated to HD mouse models.

Rights and Permissions

Citation: Lewis EA, Smith GA. Using Drosophila models of Huntington's disease as a translatable tool. J Neurosci Methods. 2016 May 30;265:89-98. doi: 10.1016/j.jneumeth.2015.07.026. PubMed PMID: 26241927. Link to article on publisher's website

Comments

First author Elizabeth Lewis is a doctoral student in the Freeman Lab and in the Neuroscience Program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.

Keywords

Candidate genes, Drosophila, Genetics, Huntington's disease, Screening

PubMed ID

26241927