Using Drosophila models of Huntington's disease as a translatable tool
Department of Neurobiology; Freeman Lab; Graduate School of Biomedical Sciences, Neuroscience Program
Genetics and Genomics | Nervous System Diseases | Neuroscience and Neurobiology
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.
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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
Candidate genes, Drosophila, Genetics, Huntington's disease, Screening
Lewis, Elizabeth A. and Smith, Gaynor A., "Using Drosophila models of Huntington's disease as a translatable tool" (2016). Freeman Lab Student Publications. 1.