BIOELECTRIC CHARACTERISTICS OF EXON-10 INSERTIONAL CYSTIC-FIBROSIS MOUSE - COMPARISON WITH HUMANS

Two important issues that can be addressed by animal models are diseas e pathogenesis and the testing of new treatments, including gene thera py. How closely these models mimic the relevant disorder in humans wil l determine their usefulness. This study examines how closely the char acteristic bioelectric features of cystic fibrosis (CF) are reproduced in the airways and intestinal tract of the exon 10 insertional mutant mouse (cf/cf). In agreement with CF subjects these cf/cf mutant mice demonstrate the following: 1) reduced adenosine 3',5'-cyclic monophosp hate-related chloride secretion throughout the respiratory and intesti nal tracts both in vivo and in vitro, 2) calcium-related chloride secr etion that is preserved in the airways but reduced in the intestine, a nd 3) a more negative nasal potential difference and increased amilori de response compared with wild-type animals, likely to relate to incre ased sodium absorption. In contrast to humans, sodium absorption is no t increased in the small intestine and is reduced in the trachea of th e cf/cf mice. We conclude that the majority of the salient electrophys iological features of CF required for studies of pathogenesis or testi ng of new treatments are present in these cf/cf mice.