Date of Award

2007

Degree Type

Thesis

Degree Name

Master of Science

Program

Biochemistry

Supervisor

Richard Rozmahel

Second Advisor

Susan Newbigging

Third Advisor

Sonya Brijbassi

Abstract

Mice deficient of the cystic fibrosis transmembrane conductance regulator exhibit a severe intestinal phenotype resulting in death generally by six weeks of age. Previous studies have shown that the severity of intestinal disease in CF mice is strongly influenced by genetic modifiers, which may impact on the CF phenotype. It is shown here that expression of mCLCA3, whose function appears to be related to mucous production and composition, is markedly reduced in CF compared to normal intestines. Moreover, correction of intestinal mCLCA3 expression to normal levels ameliorates intestinal mucous inspissation. Although the function of mCLCA3 remains unclear, its activity may relate to modification of mucous properties, thereby facilitating its clearance. Overall, these results provide further insight into physiological abnormalities underlying CF and indicate an important role for mCLCA3 in mucous based diseases. Finally, these results suggest a potential therapeutic role for the human orthologue (hCLCAl) in the human disease.

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