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.

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Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CftrRatabnormal chloride level  IMP  RGD 
Cftrem1SageRatabnormal chloride level  IMP  RGD 
SD-Cftrem1Sage-/-Ratabnormal chloride level  IMP  RGD 
CftrRatabnormal circulating protein level  IMP  RGD 
Cftrem1SageRatabnormal circulating protein level  IMP  RGD 
SD-Cftrem1Sage-/-Ratabnormal circulating protein level  IMP  RGD 
CftrRatabnormal nasal mucosa morphology  IMP  RGD 
Cftrem1SageRatabnormal nasal mucosa morphology  IMP  RGD 
SD-Cftrem1Sage-/-Ratabnormal nasal mucosa morphology  IMP  RGD 
CftrRatabnormal small intestinal villus morphology  IMP  RGD 
Cftrem1SageRatabnormal small intestinal villus morphology  IMP  RGD 
SD-Cftrem1Sage-/-Ratabnormal small intestinal villus morphology  IMP  RGD 
CftrRatabnormal tooth color  IMP  RGD 
Cftrem1SageRatabnormal tooth color  IMP  RGD 
SD-Cftrem1Sage-/-Ratabnormal tooth color  IMP  RGD 
CftrRatabnormal trachea gland morphology  IMP  RGD 
Cftrem1SageRatabnormal trachea gland morphology  IMP  RGD 
SD-Cftrem1Sage-/-Ratabnormal trachea gland morphology  IMP  RGD 
CftrRatabnormal tracheal cartilage morphology  IMP  RGD 
Cftrem1SageRatabnormal tracheal cartilage morphology  IMP  RGD 
SD-Cftrem1Sage-/-Ratabnormal tracheal cartilage morphology  IMP  RGD 
CftrRatdecreased circulating serum albumin level  IMP  RGD 
Cftrem1SageRatdecreased circulating serum albumin level  IMP  RGD 
SD-Cftrem1Sage-/-Ratdecreased circulating serum albumin level  IMP  RGD 
CftrRatdecreased T cell number  IMP  RGD 
Cftrem1SageRatdecreased T cell number  IMP  RGD 
SD-Cftrem1Sage-/-Ratdecreased T cell number  IMP  RGD 
CftrRatincreased blood urea nitrogen level  IMP  RGD 
Cftrem1SageRatincreased blood urea nitrogen level  IMP  RGD 
SD-Cftrem1Sage-/-Ratincreased blood urea nitrogen level  IMP  RGD 
CftrRatincreased neutrophil cell number  IMP  RGD 
Cftrem1SageRatincreased neutrophil cell number  IMP  RGD 
SD-Cftrem1Sage-/-Ratincreased neutrophil cell number  IMP  RGD 

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