The Role of RasGRP3 in Embryonic Response to Diabetes (2009)

Undergraduate: Jessica Heinz

Faculty Advisor: Victoria Bautch
Department: Biology

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Maternal diabetes can cause cardiovascular problems in embryos and other birth defects in humans and mice. When developing in a diabetic mother, mouse embryos are exposed to increased levels of glucose and show malformed blood vessels that lead to birth defects or death. One of the metabolites of the excess glucose is diacylglycerol (DAG) which activates Ras guanine-releasing protein 3 (RasGRP3), a guanine exchange factor important to blood vessel formation that may be related to vascular malformation when over-activated by DAG. I studied RasGRP3 in mice and its effect on mediating the malformation of blood vessels associated with developing in a diabetic environment. Using both chemical and genetic means, I induced diabetes in female mice to study the formation of embryos in diabetic environments. I isolated embryos at a time of critical vascular development, and stained their vasculature to visualize and characterize vascular and other the defects seen in the embryos from diabetic and non-diabetic mice. Wildtype embryos from a diabetic mother had many defects, however, embryos from a diabetic mother lacking RasGRP3 developed normally. This result indicates that RasGRP3 may be necessary for some of the vascular defects and other deformities associated with diabetes. This work is potentially important in understanding and developing treatments that can target certain elements of this disease pathway to prevent the birth defects associated with the diabetes.