Pathophysiology of gene-targeted mouse models for cystic fibrosis

BR Grubb, RC Boucher - Physiological reviews, 1999 - journals.physiology.org
BR Grubb, RC Boucher
Physiological reviews, 1999journals.physiology.org
Grubb, Barbara R., and Richard C. Boucher. Pathophysiology of Gene-Targeted Mouse
Models for Cystic Fibrosis. Physiol. Rev. 79, Suppl.: S193–S214, 1999.—Mutations in the
gene causing the fatal disease cystic fibrosis (CF) result in abnormal transport of several
ions across a number of epithelial tissues. In just 3 years after this gene was cloned, the first
CF mouse models were generated. The CF mouse models generated to date have provided
a wealth of information on the pathophysiology of the disease in a variety of organs …
Grubb, Barbara R., and Richard C. Boucher. Pathophysiology of Gene-Targeted Mouse Models for Cystic Fibrosis. Physiol. Rev. 79, Suppl.: S193–S214, 1999. — Mutations in the gene causing the fatal disease cystic fibrosis (CF) result in abnormal transport of several ions across a number of epithelial tissues. In just 3 years after this gene was cloned, the first CF mouse models were generated. The CF mouse models generated to date have provided a wealth of information on the pathophysiology of the disease in a variety of organs. Heterogeneity of disease in the mouse models is due to the variety of gene-targeting strategies used in the generation of the CF mouse models as well as the diversity of the murine genetic background. This paper reviews the pathophysiology in the tissues and organs (gastrointestinal, airway, hepatobiliary, pancreas, reproductive, and salivary tissue) involved in the disease in the various CF mouse models. Marked similarities to and differences from the human disease have been observed in the various murine models. Some of the CF mouse models accurately reflect the ion-transport abnormalities and disease phenotype seen in human CF patients, especially in gastrointestinal tissue. However, alterations in airway ion transport, which lead to the devastating lung disease in CF patients, appear to be largely absent in the CF mouse models. Reasons for these unexpected findings are discussed. This paper also reviews pharmacotherapeutic and gene therapeutic studies in the various mouse models.
American Physiological Society