Abstract
Mouse models for cystic fibrosis (CF) with no CFTR function(Cftr-/-) have the disadvantage that most animals die of intestinal obstruction shortly after weaning. The objective of this research was to extend the lifespan of CF mice and characterize their phenotype. Weanlings were placed on a nutrient liquid diet, and histologic and functional aspects of organs implicated in the disease were subsequently examined. Approximately 90% of Cftr-/- mice survived to 60 d, the majority beyond 100 d. Cftr-/- mice were underweight and had markedly abnormal intestinal histology. The intestinal epithelia did not respond to challenges with agents that raised intracellular cAMP, consistent with the absence of functional CFTR. No lesions or functional abnormalities were evident in the lungs. Liquid-fed Cftr-/- mice were infertile, although some males weaned to a solid diet were fertile before they died. Thus, we have succeeded in using dietary means to prolong the lives ofCftr-/- mice.
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Abbreviations
- CF:
-
cystic fibrosis
- CFTR:
-
cystic fibrosis transmembrane conductance regulator
- Cftr:
-
murine ortholog of the human gene defective in cystic fibrosis
- Isc:
-
short-circuit current
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Acknowledgements
The authors thank A. C. Bryan for helpful suggestions and for comments on the manuscript, J. Rommens for help with the manuscript, L.-J. Huan and W. F. Ip for technical assistance, and B. Koller for providing Cftr+/- mice.
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Supported by a Research Development Programme Grant (RDPIII) from the Canadian Cystic Fi-brosis Foundation.
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Kent, G., Oliver, M., Foskett, J. et al. Phenotypic Abnormalities in Long-Term Surviving Cystic Fibrosis Mice. Pediatr Res 40, 233–241 (1996). https://doi.org/10.1203/00006450-199608000-00008
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DOI: https://doi.org/10.1203/00006450-199608000-00008
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