Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Anatomy and Cell Biology

Supervisor

Dr. Dale Laird

Abstract

Using two disease-linked connexin mutant mice that possess significantly reduced connexin function (Cx43I130T/+ and Cx26K14-S17F/+) this investigation is the first to address the roles of Cx26 and Cx43 in modulating epidermal health in response to UV radiation. Viable Cx26K14-S17F/+ mice were successfully created in-house to express the mutant Cx26 S17F protein in keratinocytes and possess scaly skin, rapidly develop epidermal desquamation, and die soon after UV exposure. Conversely, Cx43I130T/+ mice did not possess any skin abnormalities before or after UV exposure. We also identified that primary murine melanocytes are not homocellularly coupled and do not express Cx43. Furthermore, we show that Cx43 may act as a tumor facilitator to promote tumor cell survival in human melanoma metastases in a variety of distant organ sites. Taken together, these studies strongly suggest that Cx26 is critical in protecting keratinocytes from acute UV damage, while Cx43 may provide melanomas with a survival advantage in distant metastases.

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