title: Glycoconjugate metabolism in a cystic fibrosis knockout mouse model.
abstract: Cystic fibrosis knockout mice (cftr(-/-)) die prematurely of obstruction of the intestine which may result from accumulation of dehydrated glycoconjugate-containing mucus. We noted an increase in the specific activity of [(14)C]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 the turnover of glycoconjugates of several organs of the cftr(-/-) mice. No difference in the anionic composition of secreted intestinal glycoconjugates 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 genotypes. In addition, the spleen of the cftr(-/-) mice was significantly smaller than that of control mice and the small intestine and colon were, respectively, longer and shorter compared to control mice. These results indicate modified glycoconjugate metabolism in cystic fibrosis knockout mice and morphologic changes to the spleen and intestine where the latter modifications are possibly related to the intestinal malabsorption associated with cystic fibrosis.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U 402, Faculté de Médecine Saint-Antoine, University Paris VI, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Mailleau
authors.forename: A
authors.initials: A
authors.lastname: Paul
authors.forename: M
authors.initials: M
authors.lastname: Colin
authors.forename: P X
authors.initials: PX
authors.lastname: Xing
authors.forename: C
authors.initials: C
authors.lastname: Guernier
authors.forename: J F
authors.initials: JF
authors.lastname: Bernaudin
authors.forename: J
authors.initials: J
authors.lastname: Capeau
authors.forename: M C
authors.initials: MC
authors.lastname: Brahimi-Horn
mesh_terms: D000818:Animals; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D003106:Colon / Q000378:metabolism; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006001:Glycoconjugates / Q000378:metabolism*; D006579:Heterozygote; D006720:Homozygote; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018396:Mucin-1 / Q000096:biosynthesis; D010179:Pancreas / Q000378:metabolism; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D014018:Tissue Distribution
chemical_list: D006001:Glycoconjugates; D018396:Mucin-1; D019005:Cystic Fibrosis Transmembrane Conductance Regulator