IN-VIVO MEASUREMENTS OF ION-TRANSPORT IN LONG-LIVING CF MICE

The Cftr (Cystic Fibrosis Transmembrane Conductance Regulator) gene co des for an epithelial chloride (C1) channel essential for fluid secret ion into the respiratory and gastrointestinal tract and from exocrine glands. Mice lacking CFTR function due to a disruption of Cftr exon 10 or exon I (Cftr(mlUNC/mlUNC) or Cftr(mlHSC/mlHSC) mice, respectively) generally suffer from severe gastrointestinal disease resulting in de ath shortly after birth or at the time of weaning. However, a subgroup of the Cftr(mlHSC/mlHSC) mice have been characterized which exhibit r elatively mild intestinal pathology resulting in a noncompromised life span compared to the more severely affected Cftr(mlUNC/mlUNC) mice. We compared the ion transport capacity of the intestinal mucosa of the m ildly and severely affected CF mice using the in viva technique of rec tal potential difference (PD) measurement and found that the net calci um-activated chloride conductance toward the lumen was much greater in the rectum of mildly affected mice than in the severely affected mice . Hence, the milder phenotype may be related to the expression of a fa ctor which enhances the net calcium-activated chloride conductance int o the lumen of the intestinal tract. (C) 1996 Academic Press, Inc.