Master of Science
Dr. Dale W. Laird
Connexin 30 (Cx30), a member of the large gap junction protein family, plays a role in the homeostasis of the epidermis and inner ear through gap junctional intercellular communication (GJIC). Here, we investigated four autosomal dominant Cx30 gene mutations linked to hearing loss and/or various skin diseases. First, the T5M mutant linked to non-syndromic hearing loss formed functional gap junction channels and hemichannels, similar to wild-type Cx30. The V37E mutant associated with keratitis-ichthyosis-deafness (KID) syndrome was retained in the endoplasmic reticulum (ER) and significantly induced unfolded protein response (UPR)-mediated apoptosis. The loss-of-function G59R mutant linked to Vohwinkel and Bart-Pumphrey syndromes was retained primarily in the Golgi apparatus. Lastly, the Clouston syndrome-linked A88V mutant significantly induced apoptosis, primarily through an UPR-independent mechanism. Collectively, we discovered that four unique Cx30 mutants cause disease through different mechanisms, highlighting the overall complexity of connexin-linked diseases and the importance of GJIC in disease prevention.
Berger, Amy C., "Skin Diseases and Non-Syndromic Hearing Loss Linked to Cx30 Mutations Arise Through Several Distinct Mechanisms" (2013). Electronic Thesis and Dissertation Repository. 1486.