Development Of A Drosophila Model Of The SCA1 Disease
Kennadi Johnson1ψ, Jordan Bryant3 ψ, Christina Comino4, Eadie Keenan4, Scoty Hearst2, Natraj Krishnan4
1Mississippi INBRE Research Scholar, Department of Biology, Tougaloo College, Tougaloo MS
2Department of Biology, Tougaloo College, Tougaloo MS
3Mathematics and Science Division, East Mississippi Community College, Golden Triangle Campus, Mayhew, MS
4Department of Biochemistry, Molecular Biology, Entomology and Plant Pathology, Mississippi State University, Mississippi State, MS
ψ Both authors contributed equally to this work
Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease characterized by progressive problems with movement. Patients affected by SCA1 develop an adult onset devastating pathology characterized by peripheral axonal motor and sensory neuropathy, distal muscular atrophy, pes cavus and steppage gait. The main goal of this summer research experience program was the development of a powerful genetic model to investigate pathogenesis of the SCA1 disease. The fruit fly, Drosophila melanogaster, is an organism extremely useful for studies on human biology, health and a wide range of pathologies including neurodegenerative diseases. This is because Drosophila genes controlling fundamental cellular functions, such as cell growth and death, are quite identical to those found in human cells. In this work, we developed a Drosophila model of the SCA1 disease by applying a well-known genetic approach. This focuses on the screening of several fly lines with UAS constructs for expression of abnormal polyglutamine repeats. The selected fly line which exhibits normal growth and development are then crossed to a Glass-multiple repeats (GMR) Gal4 line to start expression of the abnormal ataxin-1 gene encoding for polyglutamine repeats. This approach would create a fruit fly model that mimics the human pathological condition. Subsequently, genome-wide transcriptome analysis of this SCA1 fly model will provide greater insight into the mechanism of the disease. The identification of the steps of the SCA1 pathological cascade in turn will help the development of therapies targeting key molecules acting in these steps. This work was supported by the Mississippi INBRE, funded by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM103476. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of General Medical Sciences or the National Institutes of Health.