Differential Expression of Neuronal Nitric Oxide Synthase Splice Variants in Heart, Brain and Skeletal Muscle Tissues of Wild-Type Mice
Nelson C. Ugwu
Dr. Daniel E. Michele (University of Michigan), Joanne F. Garbincius (University of Michigan), and Dr. Cynthia Cooper, Faculty Mentors
Duchenne muscular dystrophy (DMD) is characterized by progressive muscle weakness, fatigue, cardiomyopathy, and early death. Abnormal exercise-induced vasodilation in DMD may result from loss of neuronal nitric oxide synthase (nNOS) function in skeletal muscle. nNOS pre-mRNA yields alternative splice variants. Their distribution in heart and skeletal muscle tissues has not been studied. Strong evidence indicates that nNOS physically binds the dystrophin-glycoprotein-complex in skeletal but not cardiac muscle. nNOS mRNA from wild-type mice brain, skeletal muscle and heart was reverse-transcribed to cDNA and PCR was used to probe for nNOS splice variants. We found that mRNA expression of alternative splice variants varied across tissues, and skeletal muscle and brain expressed multiple splice variants. These findings suggest that preferential expression of alternate splice variants in skeletal and cardiac muscle tissue could be regulatory given the different localizations of nNOS in these tissues, and may provide further insight regarding abnormal vasodilation in DMD.
Keywords: nNOS, duchenne muscular dystrophy, dystrophin glycoprotein complex, alternative splicing, skeletal muscle, cardiac muscle, dystrophin
Topic(s):Biology
Presentation Type: Poster
Session: 4-1
Location: GEO - SUB
Time: 3:30