Development of mouse models for cystic fibrosis

Abstract

Using gene targeting in embryonal stem cells it is now possible to create accurate genetic models of inherited human disease in the mouse. The value of an animal model of cystic fibrosis is in providing clarification of disease pathogenesis, genotype-phenotype correlation, the identification of other relevant genetic factors, and as the optimal test system for novel therapeutic intervention. Correction of the basic defect by a somatic gene therapy approach is an attractive approach to disease treatment. CF mouse models have been described which display the characteristic electrophysiological defect and thus both safety and efficacy can be monitored in these animals. Modulation of Cftr levels in transgenic animals and the results on disease phenotype give some indication of the level of gene expression necessary to give clinical effect.