Phenotypes of CF rabbits generated by CRISPR/Cas9-mediated disruption of the CFTR gene.

ABSTRACT: Existing animal models of cystic fibrosis (CF) have provided key insights into CF pathogenesis but have been limited by short lifespans, absence of key phenotypes, and/or high maintenance costs. Here, we report the CRISPR/Cas9-mediated generation of CF rabbits, a model with a relatively long lifespan and affordable maintenance and care costs. CF rabbits supplemented solely with oral osmotic laxative had a median survival of approximately 40 days and died of gastrointestinal disease, but therapeutic regimens directed toward restoring gastrointestinal transit extended median survival to approximately 80 days. Surrogate markers of exocrine pancreas disorders were found in CF rabbits with declining health. CFTR expression patterns in WT rabbit airways mimicked humans, with widespread distribut

SUBMITTER: Xu J 

PROVIDER: S-EPMC7821608 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature