Date of Award
Master of Science
Pharmacology and Toxicology
Dr. Dale Laird
Oculodentodigital dysplasia (ODDD) is a rare developmental disease that results from any one of over sixty known autosomal-dominant or autosomal-recessive mutations in the gene GJA1, which encodes for connexin43 (Cx43). In the current study, we assessed the characteristic of six Cx43 mutants, including two autosomal-dominant mutants which have been associated with bladder defects (D3N and G143S), two autosomal-dominant mutants which have not been associated with bladder defects (G2V and I130T) and two autosomal- recessive mutants (R33X and R76H). Collectively, we revealed no differences in the molecular or Cx43 channel function of the bladder disease -associated or -unassociated mutants suggesting that bladder defects linked to ODDD may be associated with other factors such as aging and/or co-morbidities. We also found that the R76H mutant could form functional channels while the R33X was functionally dead. These studies provide molecular insights into how autosomal dominant or recessive mutations affect Cx43 channel function and how Cx43 function may be linked to disease severity.
Lorentz, Robert James, "CHARACTERISTICS AND FUNCTION OF CONNEXIN43 MUTANTS LINKED TO OCULODENTODIGITAL DYSPLASIA" (2011). Digitized Theses. 3286.