Date of Award


Degree Type


Degree Name

Master of Science


Anatomy and Cell Biology


Dr. Dale Laird

Second Advisor

Dr. Peter Merrifield


Skeletal muscle development involves the differentiation of myoblasts into myotubes; likely involving connexins (Cx) and the gap junctional exchange of secondary messengers and metabolites. Many patients with oculodentodigital dysplasia (ODDD), a rare primarily autosomal dominant disease caused by mutations in the gene encoding Cx43, become less ambulatory with aging and exhibit symptoms that may reflect defects in skeletal muscle development, maintenance, and repair. In this study, the role of Cx43 in skeletal muscle development was examined in differentiation-competent L6 myoblasts and two ODDD- linked Cx43-mutant mouse lines. Undifferentiated L6 myoblasts exhibited high levels of Cx43-based gap junctions which were inhibited by the co-expression of IDOT and G60S mutants. Upon myotube formation, Cx43 was down-regulated and gap junctions were lost. Cx43-mutant mice heterozygous for the I130T mutation exhibited similar body weight and tibial length as littermate controls while mutant mice heterozygous for the G60S mutation were significantly smaller and had smaller muscle fibres. Overall, Cx43 regulation may be important for initial myoblast differentiation but not linked to myotube growth and while our mutant mouse studies suggest that some ODDD patients are predicted to have smaller muscle fibres, this appears to be dependent on the site of the Cx43 mutation or other unknown etiologies.



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