Cystic fibrosis mice lacking mud have reduced amounts of intestinal mucus

被引:68
作者
Parmley, RR [1 ]
Gendler, SJ [1 ]
机构
[1] Mayo Clin Scottsdale, Dept Biochem & Mol Biol, Scottsdale, AZ 85259 USA
关键词
meconium ileus; gastrointestinal tract; reverse transcription polymerase chain reaction; immunohistochemistry; mouse cystic fibrosis model;
D O I
10.1172/JCI3820
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Normally a thin layer of mucus covers the surface of the gastrointestinal tract protecting the epithelial cells from their environment. In cystic fibrosis (CF), mucus accumulation is abnormally high, resulting in severe intestinal obstruction. The major structural components of mucus are large mucin glycoproteins. We determined specific mucin RNA and protein expression in the gastrointestinal tract of inbred CF transmembrane conductance regulator (CFTR) knockout (CF) mice and correlated expression with histological analyses of tissues. Mucins were detected histochemically using general carbohydrate stains and specific mucin antibodies. Mucin RNA levels were determined by reverse transcription-PCR. Comparisons were made between CF mice and control siblings, all maintained on a liquid diet after weaning. Analyses of the mucins Muc2, Muc3, and Muc5ac showed lower levels of RNA expression in the CF mice and similar levels of protein. Significantly, there was a sixfold increase in Muc1 RNA expression in the colon of the CF mouse and a moderate increase in Mud protein. Further, CF mice lacking Mud exhibited greatly diminished intestinal mucus obstruction when compared with Muc1-expressing CF mice and had better survival on solid food. We suggest that Mud plays an important role in the mucus obstructions observed in the gastrointestinal tract of the CFTR knockout mouse.
引用
收藏
页码:1798 / 1806
页数:9
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