Department Chair

I. Martha Skerrett, Ph.D.

Date of Award

12-2015

Access Control

Campus-Only Access

Degree Name

Biology, M.A.

Department

Biology Department

Advisor

I. Martha Skerrett, Ph.D.

Department Home page

http://biology.buffalostate.edu/

First Reader

I. Martha Skerrett, Ph.D.

Second Reader

Gary W. Pettibone, Ph.D.

Third Reader

Derek L. Beahm, Ph.D.

Abstract

ABSTRACT OF THESIS

Expression and Characterization of Connexin31 Mutations Associated with

Skin Disease and Deafness

Gap junctions consist of intercellular channels that metabolically and electrically couple cells. They are found in almost all mammalian tissues. In humans, gap junction channels are composed of the connexin family of proteins and over twenty different connexins are expressed in specific but overlapping patterns in human tissue. Connexin31 (Cx31) is expressed in the skin and inner ear, and mutations in the gene encoding Cx31, GJB3, are linked to disorders of skin and hearing. To date, over thirty different Cx31 mutations have been linked to human disease. Most are missense mutations within the coding region that result in amino acid substitutions in the Cx31 protein. To better understand Cx31 mutations that cause disease, the Xenopus oocyte expression system was used in conjunction with site-directed mutagenesis and voltage clamp analysis. Three Cx31 mutants were expressed in oocytes. These include V43M, a deafness mutation, L135V a dominant skin disease mutation, and I141V which is classified as a recessive deafness mutation. Expression of V43M compromised the health of the oocytes and L135V failed to form functional channels, while I141V formed gap junction channels with characteristics very similar to those of wildtype Cx31. The results suggest that these mutations cause disease by different mechanisms. Also, to the best of our knowledge this is the first time Cx31 has been expressed in Xenopus oocytes and the first characterization of Cx31 mutations using the oocyte expression system. Our results confirm that the oocyte expression system is well suited to assess the properties of Cx31.

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