| First Author | Cohen JC | Year | 2004 |
| Journal | BMC Genet | Volume | 5 |
| Pages | 21 | PubMed ID | 15279681 |
| Mgi Jnum | J:101836 | Mgi Id | MGI:3605562 |
| Doi | 10.1186/1471-2156-5-21 | Citation | Cohen JC, et al. (2004) The 'Goldilocks effect' in cystic fibrosis: identification of a lung phenotype in the cftr knockout and heterozygous mouse. BMC Genet 5:21 |
| abstractText | BACKGROUND: Cystic Fibrosis is a pleiotropic disease in humans with primary morbidity and mortality associated with a lung disease phenotype. However, knockout in the mouse of cftr, the gene whose mutant alleles are responsible for cystic fibrosis, has previously failed to produce a readily, quantifiable lung phenotype. RESULTS: Using measurements of pulmonary mechanics, a definitive lung phenotype was demonstrated in the cftr-/- mouse. Lungs showed decreased compliance and increased airway resistance in young animals as compared to cftr+/+ littermates. These changes were noted in animals less than 60 days old, prior to any long term inflammatory effects that might occur, and are consistent with structural differences in the cftr-/- lungs. Surprisingly, the cftr+/- animals exhibited a lung phenotype distinct from either the homozygous normal or knockout genotypes. The heterozygous mice showed increased lung compliance and decreased airway resistance when compared to either homozygous phenotype, suggesting a heterozygous advantage that might explain the high frequency of this mutation in certain populations. CONCLUSIONS: In the mouse the gene dosage of cftr results in distinct differences in pulmonary mechanics of the adult. Distinct phenotypes were demonstrated in each genotype, cftr-/-, cftr +/-, and cftr+/+. These results are consistent with a developmental role for CFTR in the lung. |
