Gene structure and functional properties of mouse CRTH2, a prostaglandin D2 receptor

Gene structure and functional properties of mouse CRTH2, a prostaglandin D2 receptor
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DOI:
10.1016/s0006-291x(03)01266-x
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发表时间:
2003-08-08
影响因子:
3.1
通讯作者:
Nagata, K
Nagata, K
中科院分区:
生物学4区
文献类型:
--
作者:
Hirai, H;Abe, H;Nagata, K

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CRTH 2是前列腺素D-2(PGD(2))的第二种受体,被认为通过诱导趋化性迁移和/或激活Th 2、嗜酸性粒细胞和嗜碱性粒细胞在人类过敏性炎症中发挥作用。我们以前确定了人类CRTH 2的小鼠CRTH 2同源物,并建议动物模型将提供一个明确的理解CRTH 2在过敏性疾病中的确切功能。为此,我们已经证实,小鼠CRTH 2的基因结构与人CRTH 2相似,并揭示了小鼠CRTH 2主要表达于来源于IL-5转基因小鼠的嗜酸性粒细胞中。此外,小鼠CRTH 2具有以高亲和力结合PGD(2)的能力和以Gi依赖性方式的细胞内Ca 2+动员以及在几种转染细胞系中的趋化反应。本研究结果表明小鼠CRTH 2是人CRTH 2的功能性直系同源物,为进一步分析CRTH 2的体内功能奠定了基础。(C)2003年爱思唯尔公司All rights reserved.
CRTH2, the second receptor for prostaglandin D-2 (PGD(2)), is thought to play a role in allergic inflammations through the induction of chemotactic migration and/or the activation of Th2, eosinophils, and basophils, in humans. We previously identified the mouse CRTH2 homolog of human CRTH2 and suggest that animal models would provide a clear understanding on the precise function of CRTH2 in allergic disorders. To this end we have confirmed that mouse CRTH2 is similar in gene structure to human CRTH2 and revealed that mouse CRTH2 is predominantly expressed in the eosinophils derived from IL-5-transgenic mice. Moreover, mouse CRTH2 harbors the ability to bind PGD(2) with high affinity and intracellular Ca2+ mobilization in a Gi-dependent manner and chemotactic responses in several transfected cell lines. The results demonstrated here indicate that mouse CRTH2 is the functional ortholog of human CRTH2 and paves the way for future analysis of the in vivo functions of CRTH2. (C) 2003 Elsevier Inc. All rights reserved.