By Jada Gundy

Faculty Mentor: Ginny Morriss

Abstract

Myotonic dystrophy type 1 (DM1) is a multi-systemic condition that results in severe muscle weakening and wasting. DM1 is caused by an expanded region of CTG repeats in the DMPK gene, resulting in expression of a toxic CUG repeat-containing RNA. While the primary DM1 mutation is known, the full consequences of this mutation remain unknown. A previous study in a mouse DM1 muscle wasting model suggested that genes involved in blood vessel maintenance and development are also affected in DM1; the influx in toxic CUG repeats within DM1 causes muscle loss, associated with a reduction in the phosphorylated form of platelet derived growth receptor beta (PDGFR-β). The goal of this experiment was to determine whether specific proteins involved in blood vessel development are affected by expression of CUG repeat RNA. Within this project, human umbilical vein cells (HUVECs) expressing a segment of the DMPK RNA containing 960 CUG (CUG960) repeats were used to model DM1 blood vessels. Repeat-expressing HUVEC cells were compared to cells that expressed the same portion of DMPK without repeats (CUG0) and to cells that did not express any extra DNA (mock). The cells were given 24 hours to develop into vessels, then protein containing vascular endothelial growth factor (VEGF) and PDGFR-β were extracted from the cells. Using western blot analysis, VEGF levels and the subsequent ratio of phosphorylated PDGFR-β were measured.
The purpose of this research is to understand the role that DM1 plays in blood vessel maintenance and development, if any, and the implications that this may have for the phenotypes expressed by DM1.