Glycoconjugate metabolism in a cystic fibrosis knockout mouse model

Cystic fibrosis knockout mice (cftr(-/-)) die prematurely of obstruction of the intestine which may result from accumulation of dehydrated glycoconjug ate-containing mucus. We noted an increase in the specific activity of [C-1 4]glucosamine-labeled high-molecular weight glycoconjugates, probably mucin , in the lumen of the intestine of cftr(-/-) (homozygous) mice compared to cftr(+/+) (wild-type) and cftr(+/-) (heterozygous) mice and a decrease in t he turnover of glycoconjugates of several organs of the cftr(-/-) mice. No difference in the anionic composition of secreted intestinal glycoconjugate s was detected and no difference in the amount of mucin 1 (Muc1) was found in the small intestine, colon, pancreas, and lungs of the different genotyp es. In addition, the spleen of the cftr(-/-) mice was significantly smaller than that of control mice and the small intestine and colon were, respecti vely, longer and shorter compared to control mice. These results indicate m odified glycoconjugate metabolism in cystic fibrosis knockout mice and morp hologic changes to the spleen and intestine where the latter modifications are possibly related to the intestinal malabsorption associated with cystic fibrosis. (C) 2001 Academic Press.