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Title: Characterization of Defects in Ion Transport and Tissue Development in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-Knockout Rats
Authors: Tuggle, Katherine L.;Birket, Susan E.;Cui, Xiaoxia;Hong, Jeong;Warren, Joe;Reid, Lara;Chambers, Andre;Ji, Diana;Gamber, Kevin;Chu, Kengyeh K.;Tearney, Guillermo;Tang, Li Ping;Fortenberry, James A.;Du, Ming;Cadillac, Joan M.;Bedwell, David M.;Rowe, Steven M.;Sorscher, Eric J.;Fanucchi, Michelle V.
subject: Biology;Anatomy and Physiology;Respiratory System;Respiratory Physiology;Genetics;Human Genetics;Autosomal Recessive;Cystic Fibrosis;Model Organisms;Animal Models;Medicine;Diagnostic Medicine;Pathology;Anatomical Pathology;Histopathology;General Pathology;Molecular Pathology
Year: 2014
Publisher: Public Library of Science
Description: Animal models for cystic fibrosis (CF) have contributed significantly to our understanding of disease pathogenesis. Here we describe development and characterization of the first cystic fibrosis rat, in which the cystic fibrosis transmembrane conductance regulator gene (CFTR) was knocked out using a pair of zinc finger endonucleases (ZFN). The disrupted Cftr gene carries a 16 base pair deletion in exon 3, resulting in loss of CFTR protein expression. Breeding of heterozygous (CFTR+/−) rats resulted in Mendelian distribution of wild-type, heterozygous, and homozygous (CFTR−/−) pups. Nasal potential difference and transepithelial short circuit current measurements established a robust CF bioelectric phenotype, similar in many respects to that seen in CF patients. Young CFTR−/− rats exhibited histological abnormalities in the ileum and increased intracellular mucus in the proximal nasal septa. By six weeks of age, CFTR−/− males lacked the vas deferens bilaterally. Airway surface liquid and periciliary liquid depth were reduced, and submucosal gland size was abnormal in CFTR−/− animals. Use of ZFN based gene disruption successfully generated a CF animal model that recapitulates many aspects of human disease, and may be useful for modeling other CF genotypes, including CFTR processing defects, premature truncation alleles, and channel gating abnormalities.
Standard no: Tuggle, K. L., S. E. Birket, X. Cui, J. Hong, J. Warren, L. Reid, A. Chambers, et al. 2014. “Characterization of Defects in Ion Transport and Tissue Development in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-Knockout Rats.” PLoS ONE 9 (3): e91253. doi:10.1371/journal.pone.0091253.
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