Date of Award
2011
Degree Type
Thesis
Degree Name
Master of Science
Program
Biochemistry
Supervisor
Dr. Richard Rozmahel
Abstract
Certain mouse models of Cystic fibrosis (CF) exhibit a severe intestinal phenotype, resulting in death soon after birth or at the time o f weaning. Marked variations in intestinal disease severity among different CF mouse models have suggested a prominent role for secondary genetic modifiers ofthe disease. Calcium-activated, chloride channels (CLCA) have been postulated as genetic modifiers of CF. It has been previously shown that mCLCA3, a secreted protein involved in mucus production, shows markedly reduced expression in goblet cells o f the intestines o f a CF mouse model, and when expression is corrected through transgenic manipulation, can significantly ameliorate the disease. Current studies were undertaken using quantitative RT-PCR to show that expression of mClca6 is significantly reduced (p<0.005) in the ileum of a juvenile CF mouse model. Further quantitative RT-PCR studies were performed on the mildly-affected adult CF mice, showing significant differential expression of mClca6 in the
jejunum (p<0.005), but not in the ileum. Moreover, a CF mouse model which exhibits relatively mild lung and intestinal disease compared to other mouse models shows no significant differential expression of mClca6 in the ileum. Although the function of mCLCA6 remains unclear, these results provide support for it as a potential modifier of intestinal disease severity
Recommended Citation
Mount, Gillian Rebecca, "Investigation of murine calcium-activated, chloride channel 6 as a potential modifier of Cystic fibrosis intestinal disease in mice" (2011). Digitized Theses. 3656.
https://ir.lib.uwo.ca/digitizedtheses/3656