title: Phenotypic abnormalities in long-term surviving cystic fibrosis mice.
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 of Cftr-/- mice.
authors.affiliation: Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Kent
authors.forename: M
authors.initials: M
authors.lastname: Oliver
authors.forename: J K
authors.initials: JK
authors.lastname: Foskett
authors.forename: H
authors.initials: H
authors.lastname: Frndova
authors.forename: P
authors.initials: P
authors.lastname: Durie
authors.forename: J
authors.initials: J
authors.lastname: Forstner
authors.forename: G G
authors.initials: GG
authors.lastname: Forstner
authors.forename: J R
authors.initials: JR
authors.lastname: Riordan
authors.forename: D
authors.initials: D
authors.lastname: Percy
authors.forename: M
authors.initials: M
authors.lastname: Buchwald
mesh_terms: D000818:Animals; D003550:Cystic Fibrosis / Q000235:genetics* / Q000473:pathology; D004032:Diet; D004195:Disease Models, Animal; D005260:Female; D005835:Genitalia / Q000473:pathology*; D007422:Intestines / Q000473:pathology*; D008136:Longevity; D008297:Male; D051379:Mice; D018181:Mice, Inbred CFTR; D010179:Pancreas / Q000473:pathology; D010641:Phenotype; D012137:Respiratory System / Q000473:pathology*