Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice:: Mutations in Tlr4 gene
Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice:: Mutations in Tlr4 gene
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DOI：
10.1126/science.282.5396.2085
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发表时间：
1998-12-11
期刊：
影响因子：
56.9
通讯作者：
Beutler, B
中科院分区：
文献类型：
--
作者：
Poltorak, A;He, XL;Beutler, B
Lps基因的突变选择性地阻碍C3 H/HeJ和C57 BL/10 ScCr小鼠中的脂多糖（LPS）信号转导，使它们对内毒素具有抗性，但对革兰氏阴性菌感染高度敏感。C3 H/HeJ小鼠的共显性Lps（d）等位基因显示对应于Toll样受体-4基因（Tlr 4）第三外显子中的错义突变，预测在多肽链的第712位用组氨酸取代脯氨酸。C57 BL/10 ScCr小鼠是Tlr 4无效突变的纯合小鼠。因此，哺乳动物Tlr 4蛋白已主要适应于辅助LPS的识别，并可能跨血浆转导LPS信号。TLR 4的破坏性突变容易导致革兰氏阴性脓毒症的发生，使免疫功能的大部分方面保持完整。
Mutations of the gene Lps selectively impede Lipopolysaccharide (LPS) signal transduction in C3H/HeJ and C57BL/10ScCr mice, rendering them resistant to endotoxin yet highly susceptible to Gram-negative infection. The codominant Lps(d) allele of C3H/HeJ mice was shown to correspond to a missense mutation in the third exon of the Toll-Like receptor-4 gene (Tlr4), predicted to replace proline with histidine at position 712 of the polypeptide chain. C57BL/10ScCr mice are homozygous for a null mutation of Tlr4, Thus, the mammalian Tlr4 protein has been adapted primarily to subserve the recognition of LPS and presumably transduces the LPS signal across the plasm a mem bra ne. Destructive mutations of Tlr4 predispose to the development of Gram-negative sepsis, Leaving most aspects of immune function intact.