DIETARY-CHANGES IMPROVE SURVIVAL OF CFTR S489X HOMOZYGOUS MUTANT MOUSE

Over 90% of untreated CFTR S489X homozygous (CF) mutant mice reportedl y die of intestinal obstruction by 40 days of age, significantly limit ing their usefulness as a model for the human disease. Because the per iod of highest mortality is during the week after weaning, we hypothes ized that providing a low-residue liquid diet would improve survival a nd growth. When 99 CF mice that survived to 10 days of age were fed Pe ptamen (Clintec Nutrition), an elemental liquid diet, and housed on co rn-cob bedding, 88% of them survived to maturity (50 days). The diet c auses only minor histologic and ion transport changes in the intestine s of normal mice and does not reduce growth rate or size. CF mice rais ed on Peptamen continue to display severe pathological changes in the intestine and completely lack a adenosine 3',5'-cyclic monophosphate-i nducible chloride current in the cecum. This combination of dietary an d bedding changes provides a reliable method for keeping CF mice alive well into adulthood and will be useful for the evaluation of the effe ct and duration of potential therapies for CF.