FATE OF Cx43 IN CARDIAC AND EPIDERMAL TISSUES HARBOURING A DISEASE-LINKED Cx43 MUTANT

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.

Name thesis:degree_name

M Sc

Discipline thesis:degree_discipline

Physiology

Year dc:date.issued

2007

Author dc:creator

• Manias, Janet L.

Advisor dc:contributor.advisor

• Laird, Dale

• connexin43
• gap junction
• oculodentodigital dysplasia
• mouse model
• cardiomyocyte
• keratinocyte

Handle dc:identifier.uri

https://hdl.handle.net/20.500.14721/20460

OAI identifier oai:identifier

oai:uwo.scholaris.ca:20.500.14721/20460