Title

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

Student Author(s)

Elizabeth Lewis

Academic Program

Neuroscience

UMMS Affiliation

Department of Neurobiology; Freeman Lab; Graduate School of Biomedical Sciences

Publication Date

2015-08-01

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Animal Experimentation and Research | Computational Biology | Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Genetic Phenomena | Genetics | Genomics | Mental Disorders | Molecular and Cellular Neuroscience | Molecular Genetics | Nervous System | Nervous System Diseases | Pathology

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.

Keywords

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

DOI of Published Version

10.1016/j.jneumeth.2015.07.026

Source

J Neurosci Methods. 2015 Aug 1. pii: S0165-0270(15)00281-2. doi: 10.1016/j.jneumeth.2015.07.026. [Epub ahead of print] Link to article on publisher's site

Journal/Book/Conference Title

Journal of neuroscience methods

Related Resources

Link to Article in PubMed

PubMed ID

26241927

Link to Full Text

Share

COinS