RGD Reference Report - Characterization of defects in ion transport and tissue development in cystic fibrosis transmembrane conductance regulator (CFTR)-knockout rats. - Rat Genome Database

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Characterization of defects in ion transport and tissue development in cystic fibrosis transmembrane conductance regulator (CFTR)-knockout rats.

Authors: Tuggle, KL  Birket, SE  Cui, X  Hong, J  Warren, J  Reid, L  Chambers, A  Ji, D  Gamber, K  Chu, KK  Tearney, G  Tang, LP  Fortenberry, JA  Du, M  Cadillac, JM  Bedwell, DM  Rowe, SM  Sorscher, EJ  Fanucchi, MV 
Citation: Tuggle KL, etal., PLoS One. 2014 Mar 7;9(3):e91253. doi: 10.1371/journal.pone.0091253. eCollection 2014.
RGD ID: 11566051
Pubmed: PMID:24608905   (View Abstract at PubMed)
PMCID: PMC3946746   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0091253   (Journal Full-text)

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.

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Cftr  (CF transmembrane conductance regulator)
Cftrem1Sage  (cystic fibrosis transmembrane conductance regulator; ZFN induced mutant 1 Sage)

Genes (Mus musculus)
Cftr  (cystic fibrosis transmembrane conductance regulator)

Genes (Homo sapiens)
CFTR  (CF transmembrane conductance regulator)

SD-Cftrem1Sage-/-  (NA)

Additional Information