Transgenic laboratory animals in cystic fibrosis research

Abstract

Cystic fibrosis (CF) is the most common fatal autosomal recessive genetic disorder in Caucasian populations. The incidence in Denmark is approximately 1:4500 and about 50.000 CF patients are registred in Europe and the Americas.The disease
is characterized by malabsorption due to exocrine pancreatic insufficiency, chronic bacterial infections in the lower respiratory tract, increased salt loss in sweat, and male infertility due to absence or stenosis of the vas deferens. The CF gene was
identified on Chromosome 7 in 1989. More than 450 different mutations have been detected, the most common being the AF508.This gene encodes for the cystic fibrosis transmembrane regulator protein (CFTR) which is a Cl' channel regulated
by protein kinase C and ATP. It facilitates transport of Cl' and other ions through the cell membrane. Two years ago. three different groups of scientists published articles describing three different variants of CF mice (>>knock—out<< mice).
Two of these mice suffer from severe CF-like symptoms. especially in the intestine. and most of them die within 3 weeks. The last one has some residual CFTR activity and survives for several months. These mice allow investigations on gene
therapy using different vectors and investigations on the pathogenesis of the chronic Pseudomonas aeruginosa lung infection to be carried out. Thus. the prospects for understanding CF seems promising.