Structural, expression, and evolutionary analysis of mouse CIASI
Structural, expression, and evolutionary analysis of mouse CIASI
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DOI：
10.1016/j.gene.2004.05.002
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发表时间：
2004-08-18
期刊：
影响因子：
3.5
通讯作者：
Hoffman, HM
中科院分区：
文献类型：
--
作者：
Anderson, JP;Mueller, JL;Hoffman, HM
人类CIAS1 （hCIAS1）基因突变已在一系列炎症性疾病中被发现，包括家族性感冒自身炎症综合征（FCAS）、Muckle-Wells综合征（MWS）和新生儿发病多系统炎症性疾病（NOMID）。CIAS1编码Cryopyrin蛋白，Cryopyrin似乎通过调节促炎细胞因子的产生在先天免疫功能中发挥作用。人和小鼠Cryopyrin是高度保守的，由三个功能域组成，包括pyrin结构域、NACHT结构域和富含亮氨酸的重复（LRR）结构域，这些结构域是NALP蛋白家族的特征。Cryopyrin和其他NALP蛋白的pyrin和NACHT结构域在灵长类动物和非灵长类动物中高度保守，表明在哺乳动物进化过程中存在纯化选择。Cryopyrin在人和小鼠中的表达也非常相似，小鼠主要在外周血白细胞中发现CIAS1 mRNA表达，这与假设的炎症功能一致。我们还在小鼠眼睛和皮肤组织中检测到显著的表达，这与在人类cryopyrin相关疾病中观察到的症状一致。(C) 2004 Elsevier B.V.版权所有
Mutations in the human CIAS1 (hCIAS1) gene have been identified in a continuum of inflammatory disorders including familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal onset multisystem inflammatory disease (NOMID). CIAS1 codes for the protein Cryopyrin, which appears to play a role in innate immune function by regulating the production of proinflammatory cytokines. Human and mouse Cryopyrin are highly conserved and consist of three functional domains including a pyrin domain, an NACHT domain, and a leucine-rich repeat (LRR) domain that are characteristics of the NALP family of proteins. The pyrin and NACHT domains of Cryopyrin and other NALP proteins are highly conserved among primate and nonprimate mammals, suggesting purifying selection throughout mammalian evolution. Cryopyrin expression is also very similar in human and mouse with mouse CIAS1 mRNA expression found primarily in peripheral blood leukocytes consistent with the postulated inflammatory function. We also detected significant expression in mouse eye and skin tissue, which is consistent with symptoms observed in human Cryopyrin-associated diseases. (C) 2004 Elsevier B.V. All rights reserved.