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Genetic variation and activity of mouse Nod2, a susceptibility gene for Crohn's disease small star, filled.

机译:小鼠Nod2(克罗恩氏病小星的易感基因)的遗传变异和活性得到了填补。

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摘要

Genetic variation in human Nod2 has been associated with susceptibility to Crohn's disease. The mouse Nod2 locus is located at chromosome 8 and composed of 12 exons, 11 of which encode the Nod2 protein. Sequence analysis of Nod2 from 45 different strains of Mus musculus and Mus spretus revealed extensive polymorphism involving all exons of Nod2. Of the 140 polymorphic sites identified, 68 were located in the coding region, of which 28 created amino acid substitutions in Nod2. Expression of mouse Nod2 activated NF-kappaB and conferred responsiveness to bacterial components, an activity that was deficient in mutants corresponding to those associated with susceptibility to Crohn's disease. These studies demonstrate a conserved role for Nod2 in the response to bacterial components and suggest that selective evolutionary pressure exerted by pathogens may have contributed to the high level of variability of Nod2 sequences in both humans and mice.
机译:人类Nod2的遗传变异与克罗恩氏病的易感性有关。小鼠Nod2基因座位于8号染色体上,由12个外显子组成,其中11个外显子编码Nod2蛋白。对来自Mus musmus和spretus的45种不同菌株的Nod2进行的序列分析显示,Nod2的所有外显子都有广泛的多态性。在鉴定的140个多态位点中,有68个位于编码区,其中28个在Nod2中产生了氨基酸取代。小鼠Nod2的表达激活了NF-κB并赋予了对细菌成分的响应性,这种活性在对应于与克罗恩氏病易感性相关的突变体中缺乏。这些研究证明了Nod2在对细菌成分的应答中的保守作用,并表明病原体施加的选择性进化压力可能有助于人和小鼠中Nod2序列的高水平变异性。

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