Date of Award
2007
Degree Type
Thesis
Degree Name
Master of Science
Program
Physiology
Supervisor
Dr. Dale Laird
Abstract
Mutations in the GJA1 gene encoding Cx43 are linked to oculodentodigital dysplasia (ODDD), a pleiotropic, autosomal dominant disorder. We hypothesized that in the Gjal54 mouse model of ODDD there would be significant down-regulation of total Cx43 yet minimal compromise to cardiomyocyte or kératinocyte function. Cardiac and epidermal tissue from Gjal* mice revealed a 60-75% reduction in Cx43 protein. Compensation via the up-regulation of Cx40 or Cx45 was not observed in the heart and there was a concurrent 75% down-regulation of Cx26 in the skin. Immunohistochemistry revealed a trafficking defect, with a population of Cx43 retained in the Golgi apparatus. Despite the decrease in Cx43, cardiomyocytes from Gjal5* mice show normal dye coupling and synchronous beating. However, dye coupling between keratinocytes from Gjal5 mice was significantly reduced yet an intact stratified epidermis was maintained. These results suggest that in wild type mice Cx43 may be biosynthesized in excess of what is necessary to sustain cardiac and epidermal tissue function.
Recommended Citation
Manias, Janet L., "FATE OF Cx43 IN CARDIAC AND EPIDERMAL TISSUES HARBOURING A DISEASE-LINKED Cx43 MUTANT" (2007). Digitized Theses. 5109.
https://ir.lib.uwo.ca/digitizedtheses/5109