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Publication : Intestinal phenotype of variable-weight cystic fibrosis knockout mice.

First Author  Canale-Zambrano JC Year  2007
Journal  Am J Physiol Gastrointest Liver Physiol Volume  293
Issue  1 Pages  G222-9
PubMed ID  17615178 Mgi Jnum  J:123741
Mgi Id  MGI:3719349 Doi  10.1152/ajpgi.00405.2006
Citation  Canale-Zambrano JC, et al. (2007) Intestinal phenotype of variable-weight cystic fibrosis knockout mice. Am J Physiol Gastrointest Liver Physiol 293(1):G222-9
abstractText  Cystic fibrosis (CF) transmembrane conductance regulator (Cftr) knockout mice present the clinical features of low body weight and intestinal disease permitting an assessment of the interrelatedness of these phenotypes in a controlled environment. To identify intestinal alterations that are affected by body weight in CF mice, the histological phenotypes of crypt-villus axis height, goblet cell hyperplasia, mast cell infiltrate, crypt cell proliferation, and apoptosis were measured in a population of 12-wk-old (C57BL/6 x BALB/cJ) F2 Cftr(tm1UNC) and non-CF mice presenting a range of body weight. In addition, cardiac blood samples were assessed, and gene expression profiling of the ileum was completed. Crypt-villus axis height decreased with increasing body weight in CF but not control mice. Intestinal crypts from CF mice had fewer apoptotic cells, per unit length, than did non-CF mice, and normalized cell proliferation was similar to control levels. Goblet cell hyperplasia and mast cell infiltration were increased in the CF intestine and identified to be independent of body weight. Blood triglyceride levels were found to be significantly lower in CF mice than in control mice but were not dependent on CF mouse weight. By expression profiling, genes of DNA replication and lipid metabolism were among those altered in CF mice relative to non-CF controls, and no differences in gene expression were measured between samples from CF mice in the 25th and 75th percentile for weight. In this CF mouse model, crypt elongation, due to an expanded proliferative zone and decreased apoptosis, was identified to be dependent on body weight.
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