Dietary changes improve survival of CFTR S489X homozygous mutant mouse

Abstract

Over 90% of untreated CFTR S489X homozygous (CF) mutant mice reportedly die of intestinal obstruction by 40 days of age, significantly limiting their usefulness as a model for the human disease. Because the period of highest mortality is during the week after weaning, we hypothesized that providing a low-residue liquid diet would improve survival and growth. When 99 CF mice that survived to 10 days of age were fed Peptamen (Clintec Nutrition), an elemental liquid diet, and housed on corn-cob bedding, 88% of them survived to maturity (50 days). The diet causes only minor histologic and ion transport changes in the intestines of normal mice and does not reduce growth rate or size. CF mice raised on Peptamen continue to display severe pathological changes in the intestine and completely lack a adenosine 3',5'-cyclic monophosphate-inducible chloride current in the cecum. This combination of dietary and bedding changes provides a reliable method for keeping CF mice alive well into adulthood and will be useful for the evaluation of the effect and duration of potential therapies for CF.

Impact of Nutrition on Phenotype in CFTR-deficient Mice

“…The administration of Peptamen, an easily digestible low-residue liquid diet, was first proposed by Eckman et al (11) to prevent intestinal obstruction. These authors demonstrated that this liquid diet markedly increased the lifespan in Cftr -/-mice, and that 88% of treated mice reached maturity.…”

No indications for altered essential fatty acid metabolism in two murine models for cystic fibrosis

“…Weaning on a complete elemental liquid diet, such as Peptamen, significantly improves survival rates, but CF mice fed Peptamen remain considerably smaller than with normal littermates. To meet daily caloric needs, adult mice have to consume up to 15 ml of Peptamen per day (28), and lower intake may result in malnutrition. Striking similarities have been described between Peptamen-fed cftr Ϫ/ϪUNC mice and a malnourished CF mouse model regarding pulmonary cytokine profiles (30), suggesting that malnutrition secondary to liquid diet feeding may contribute to symptoms in Peptamen-fed CF mice (29).…”

Assessment of cystic fibrosis transmembrane conductance regulator (CFTR) activity in CFTR-null mice after bone marrow transplantation

“…To allow CFTRϪ͞Ϫ mice to reach adulthood, they were fed with 9F food (Teklad, Madison, WI) and the drinking water was supplemented with 17.5 g͞250 ml of Colyte (Schwarz Pharma, Milwaukee, WI). Mice that underwent BM transplantation were fed a liquid diet of Peptamen (Nestle clinical nutritional product, Breinigsville, PA) (25). All procedures were performed in compliance with relevant laws and institutional guidelines and were approved by the Yale University Institutional Animal Care and Use Committee.…”