By Eleni Kepler

Faculty Mentor: Dr. Ginny Morriss

Abstract

Myotonic Dystrophy Type One (DM1) is a multi-systemic disorder caused by the repeat expansion of a CTG sequence in the DMPK gene that is primarily characterized by low muscle tone. Another common symptom of DM1 is insulin resistance caused by aberrant splicing of the insulin receptor in skeletal muscle (INSR), which can often develop into Type Two Diabetes. While the cause and features of DM1 are known, there is no known cure and very few effective treatments. If muscle growth is facilitated, some of the symptoms of DM1 may be alleviated. Myostatin, a muscle-secreted cytokine, both presents as a biomarker for and regulates muscle growth. In Drosophila melanogaster, the homolog of myostatin is myoglianin, coded by the myo gene. Our lab uses a Drosophila DM1 model that expresses expanded CUG repeat RNA using the Gal4/UAS system and modulates the expression of myo by RNAi knockdown. Preliminary data from this study suggests that expression of expanded CUG repeats significantly decreases climbing ability, measured by climbing velocity (cm/sec). Successful knockdown of myo has been confirmed via RT-qPCR and genes encoding components of the INSR transduction pathway show reduced RNA expression. The flies from this experiment will be assessed for whether myo knockdown can alleviate muscle function phenotypes in DM1 flies and how signaling of the insulin pathway is affected by the knockdown of myo in our DM1 model.