By Jessica Bronski, Madison Bauserman

Faculty Mentor: Dr. Ginny Morriss

Abstract

Myotonic dystrophy 1 (DM1) is a genetic disease that affects multiple organ systems including skeletal musculature, in which it causes muscle wasting. DM1 is caused by expanded CTG repeats in the 3’ untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. Capillaries are essential for nutrient delivery and waste clearance in skeletal muscle. Skeletal myoblast cells were infected with either a plasmid containing 0 CTG repeats and one with 960 CTG repeats. Both plasmids were under the control of a bidirectional tetracycline inducible promoter (BITET) in order to visualize and mimic effects of DM1. Previously unpublished data from our lab on human umbilical vein endothelial cells (HUVEC cells) transfected with expanded CTG repeat plasmids were analyzed. They displayed severe endothelial tube degradation based on length and width measurements. HUVEC cells transfected with 0 CTG repeats exhibit markedly less degradation. Potential future studies would investigate the role of a chemical PDGF-BB that plays a role in how skeletal muscle and capillaries communicate. Platelet derived growth factor receptor β (PDGFRβ), when bound to PDGF-BB, induces angiogenesis. In a mouse model of DM1, PDGFRβ signaling was found to be deregulated. Poses potential for decreased degradation of endothelial tubes affected with DM1.