Cystic fibrosis mice lacking mud have reduced amounts of intestinal mucus
Cystic fibrosis mice lacking mud have reduced amounts of intestinal mucus
复制标题
DOI：
10.1172/jci3820
复制
发表时间：
1998-11-15
影响因子：
15.9
通讯作者：
Gendler, SJ
中科院分区：
文献类型：
--
作者：
Parmley, RR;Gendler, SJ
正常情况下，一层薄薄的粘液覆盖在胃肠道的表面，保护上皮细胞免受环境的影响。在囊性纤维化（CF）中，粘液积聚异常高，导致严重的肠梗阻。粘液的主要结构成分是大粘蛋白糖蛋白。我们确定了特定的粘蛋白的RNA和蛋白质的表达在近交系CF跨膜传导调节因子（CFTR）基因敲除（CF）小鼠的胃肠道和相关的表达与组织的组织学分析。用组织化学方法检测粘蛋白，使用一般的碳水化合物染色和特异性粘蛋白抗体。通过逆转录-PCR测定粘蛋白RNA水平。在CF小鼠和对照同胞之间进行了比较，所有小鼠在断奶后都保持流质饮食。对粘蛋白Muc 2、Muc 3和Muc 5ac的分析显示，CF小鼠的RNA表达水平较低，蛋白质水平相似。值得注意的是，CF小鼠结肠中Muc 1 RNA表达增加了6倍，Mud蛋白中度增加。此外，与表达Muc 1的CF小鼠相比，缺乏Mud的CF小鼠表现出大大减少的肠粘液阻塞，并且在固体食物下具有更好的存活率。我们认为，泥起着重要的作用，在CFTR基因敲除小鼠胃肠道中观察到的粘液阻塞。
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.