Date of Award:
Doctor of Philosophy (PhD)
Animal, Dairy, and Veterinary Sciences
Irina A. Polejaeva (Committee Chair), Kenneth L. White (Committee Co-chair)
Irina A. Polejaeva
Kenneth L. White
Cystic Fibrosis (CF) is a genetic disease that affects over 80,000 people worldwide and is caused by mutations that disrupt the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. This gene encodes a channel protein that regulates ion transport in cells. The most common mutation in the human CFTR gene is F508del, which is characterized by the deletion of a phenylalanine amino acid in the CFTR protein. The second most common mutation is G542X, a protein synthesis “stop” mutation that prevents the production of the CFTR channel protein. An impediment that prevents the further understanding CF is the limited ability of most animal models to recapitulate some aspects of CF observed in humans. Sheep be a relevant animal model for CF due to the similarity of CFTR gene/protein, anatomy, physiology, body weight, and size between sheep and humans.
We hypothesized that a sheep models of CF disease could replicate the severe abnormalities seen in human CF patients. Our CF sheep models exhibit severe abnormalities consistent with CF pathology in human patients. The primary cause of death of CF sheep is the intestinal obstruction that occurred in all CF lambs. Thereby, we aimed to genetically modify CF sheep to create animal models to better understand initiation and progression of CF and for the discovery of new therapeutics to treat CF patients.
Périssé, Iuri Viótti, "Generation of Sheep Models of Cystic Fibrosis by Gene Editing and Cloning" (2021). All Graduate Theses and Dissertations. 8136.
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