Master of Science
Physiology and Pharmacology
Dr. Dale W. Laird
Connexin26 (Cx26) and Cx30 facilitate gap junctional intercellular communication (GJIC) in the epidermis and are linked to several syndromic skin diseases. We investigated 5 disease- linked Cx26 mutants and demonstrated that the severity and extent of disease can be predicted from the gain- or loss-of function properties of each mutant, as well as the ability to induce cell death. We also used transgenic mice expressing S17F Cx26 (linked to keratitis-ichthyosis- deafness syndrome) or A88V Cx30 (linked to Clouston Syndrome) to investigate the pathophysiology these skin diseases. We demonstrated that S17F Cx26, but not A88V Cx30, promotes palmoplantar keratoderma by disrupting keratinocyte differentiation. Primary keratinocyte cultures from these mice demonstrated the mutants can also affect gap junctional intercellular communication and cell migration. Lastly, we showed that mutant mice retain most wound healing properties. Together, we suggest that syndromic mutants often display gain-of-function properties and can disrupt keratinocyte differentiation in the epidermis.
Press, Eric R., "Insights into the role of connexin26 and connexin30 in skin health, syndromic disease, and cutaneous wound healing" (2016). Electronic Thesis and Dissertation Repository. 4286.