By Carleigh Wood

Faculty Mentor: Dr. Ginny Morriss

Abstract

This research investigated Drosophila melanogaster’s ability to serve as a model organism for the neurological phenotypes of Myotonic Dystrophy Type I (DM1). DM1 is caused by a CTG repeat expansion in the DMPK gene. DM1 leads to symptoms of muscle weakness and wasting, as well as decreased volumes of white and gray matter in the brain. This study aimed to determine whether DM1-affected Drosophila exhibit neurological changes, as has been observed in humans. Healthy control (CUG20) and DM1-affected Drosophila (CUG250) were generated using classical genetics. Both groups were aged three weeks prior to dissection and imaged through fluorescent microscopy. It was predicted that Drosophila melanogaster affected by DM1 would have lower cerebral volume and decreased neuronal number, relative to healthy controls. Fluorescent microscopy showed a slight, though non-significant, decrease in cell body number and Tyrosine Hydroxylase expression in DM1-affected flies, compared to healthy controls. Furthermore, as neurotrophic factors are known to exert a neuroprotective effect against neurodegenerative disease through increasing neuroplasticity, the differences in the levels of these factors between healthy controls and DM1-affected Drosophila was investigated. RT-qPCR was used to investigate the levels of the Irisin homolog, Iditarod, and the BDNF ortholog, DNT1, in Drosophila brain tissue. It was predicted that CTG250 flies would exhibit lower levels of these protective factors. Optimization of these assays is ongoing. This study concluded that DM1-affected Drosophila showed slight, but not significant, differences in neurological structure compared to healthy controls. Therefore, the study merits future optimization and investigation to reach a robust understanding of Drosophila’s suitability as a model organism for the neurological phenotypes of DM1.