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Sheep Models Of F508del And G542x Cystic Fibrosis Mutations Show Cellular Responses To Human Therapeutics, Iuri Viótti Périssé, Zhiqiang Fan, Arnaud J. Van Wettere, Ying Liu, Shih-Hsing Leir, Jacob Keim, Misha Regouski, Michael D. Wilson, Kelly M. Cholewa, Sara N. Mansback, Thomas J. Kelly, Zhongde Wang, Ann Harris, Kenneth L. White, Irina A. Polejaeva

Animal, Dairy, and Veterinary Science Student Research

Cystic Fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. The F508del and G542X are the most common mutations found in US patients, accounting for 86.4% and 4.6% of all mutations, respectively. The F508del causes deletion of the phenylalanine residue at position 508 and is associated with impaired CFTR protein folding. The G542X is a nonsense mutation that introduces a stop codon into the mRNA, thus preventing normal CFTR protein synthesis. Here, we describe the generation of CFTRF^{508del/F508del} and CFTR^G542X/G542X lambs using CRISPR/Cas9 and …