Department Chair

Daniel L. Potts, Ph.D.

Date of Award


Access Control

Open Access

Degree Name

Biology, M.A.


Biology Department


I. Martha Skerrett, Ph.D.

Department Home page

First Reader

I. Martha Skerrett, Ph.D.

Second Reader

Derek L. Beahm, Ph.D.

Third Reader

Gregory J. Wadsworth, Ph.D


At least five beta-type connexins are expressed in various layers of the skin (Cx26, Cx30, Cx30.3, Cx31, and Cx32) and all include a glycine residue at position 12. Glycine12 (G12) is located about halfway through the cytoplasmic amino terminus and has been the focus of several studies related to connexin diseases and gap junction channel structure. The importance of this residue is evident in the severity and diversity of diseases associated with amino acid substitutions at G12 including hereditary forms of skin disease, deafness and neuropathy. This study uses bioinformatic analysis in combination with mutational analysis and electrophysiology to better understand the importance of G12. Sequence alignments revealed that G12 is one of only three conserved glycine residues in beta-type connexins of skin. The functional consequences of mutations at position G12 were investigated through expression and characterization in Xenopus oocytes. Three disease-associated mutants were created and expressed including Cx31G12D, Cx31G12R and Cx32G12S. Cx31G12D induced cell death through a mechanism that was mildly calcium-sensitive. Cx31G12R and Cx32G12S drastically reduced the formation of functional intercellular channels. These data are consistent with other studies reporting a variety of functional consequences when G12 is altered in beta-type connexins.