PHENOTYPIC ABNORMALITIES IN LONG-TERM SURVIVING CYSTIC-FIBROSIS MICE

Mouse models for cystic fibrosis (CF) with no CFTR function (Cftr(-/-) ) have the disadvantage that most animals die of intestinal obstructio n shortly after weaning. The objective of this research was to extend the lifespan of CF mice and characterize their phenotype. Weanlings we re placed on a nutrient liquid diet, and histologic and functional asp ects of organs implicated in the disease were subsequently examined. A pproximately 90% of Cftr(-/-) mice survived to 60 d, the majority beyo nd 100 d. Cftr(-/-) mice were underweight and had markedly abnormal in testinal histology. The intestinal epithelia did not respond to challe nges with agents that raised intracellular cAMP, consistent with the a bsence of functional CFTR. No lesions or functional abnormalities were evident in the lungs. Liquid-fed Cftr(-/-) mice were infertile, altho ugh some males weaned to a solid diet were fertile before they died. T hus, we have succeeded in using dietary means to prolong the lives of Cftr(-/-) mice.