By Eleni Kepler

Faculty Mentor: Dr. Ginny Morriss

Abstract

Myotonic Dystrophy Type One (DM1) is a multisystemic disorder caused by a CTG repeat expansion in DMPK that is characterized primarily by low muscle tone. Another common symptom of DM1 is insulin resistance due to 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. Assessment of the expression of proteins downstream of INSR activations has started. Thus far, we have successfully reduced muscle function as seen in DM1 through repeat expansion and will go on to assess atrophy.