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人源和鼠源中N-甲酰肽受体基因簇的差异扩增

Differential expansion of the N-formylpeptide receptor gene cluster in human and mouse.

作者信息

Gao J L, Chen H, Filie J D, Kozak C A, Murphy P M

机构信息

Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.

出版信息

Genomics. 1998 Jul 15;51(2):270-6. doi: 10.1006/geno.1998.5376.

DOI:10.1006/geno.1998.5376
PMID:9722950
Abstract

The human formylpeptide receptor (FPR) gene cluster has three members: FPR1 and FPRL1, which are expressed in neutrophils and monocytes and encode seven-transmembrane-domain chemotactic receptors specific for N-formylpeptides, and FPRL2, whose function is unknown. The FPRL1 receptor is also a lipoxin A4 receptor. Using probes for the three human genes we have cloned six distinct mouse genes, designated Fpr1 and Fpr-rs1 through Fpr-rs5, which form a cluster on chromosome 17 in a region of conserved synteny with human chromosome 19. Fpr1 encodes a functional receptor and is clearly the orthologue of FPR1. Both Fpr-rs1 and Fpr-rs2 have higher sequence homology to FPRL1 than to FPRL2; Fpr-rs1 is 97% identical in amino acid sequence to a previously reported cDNA that encodes a lipoxin A4 receptor, whereas the putative ligand for Fpr-rs2 is unknown. Fpr-rs3, Fpr-rs4, and Fpr-rs5 appear to lack human counterparts and are most similar in sequence to FPRL1. RNA for Fpr1, Fpr-rs1, and Fpr-rs2 is present in leukocytes, spleen, and lung, whereas RNA for Fpr-rs3 was detected only in skeletal muscle. We did not detect Fpr-rs4 or Fpr-rs5 RNA in any tissue tested. Moreover, Fpr-rs5 has a stop codon in the protein-coding region corresponding to transmembrane domain VI and may not encode a functional receptor. These results suggest that the FPR gene cluster has undergone differential expansion in mammals with FPRL2, Fpr-rs2, Fpr-rs3, Fpr-rs4, and Fpr-rs5 arising after divergence of human and mouse.

摘要

人类甲酰肽受体(FPR)基因簇有三个成员:FPR1和FPRL1,它们在中性粒细胞和单核细胞中表达,编码对N-甲酰肽具有特异性的七跨膜结构域趋化受体;以及功能未知的FPRL2。FPRL1受体也是脂氧素A4受体。利用针对这三个人类基因的探针,我们克隆了六个不同的小鼠基因,命名为Fpr1和Fpr-rs1至Fpr-rs5,它们在17号染色体上形成一个基因簇,位于与人类19号染色体同源的保守区域。Fpr1编码一种功能性受体,显然是FPR1的直向同源物。Fpr-rs1和Fpr-rs2与FPRL1的序列同源性高于与FPRL2的同源性;Fpr-rs1的氨基酸序列与先前报道的编码脂氧素A4受体的cDNA有97%的同一性,而Fpr-rs2的推定配体未知。Fpr-rs3、Fpr-rs4和Fpr-rs5似乎没有人类对应物,并且在序列上与FPRL1最相似。Fpr1、Fpr-rs1和Fpr-rs2的RNA存在于白细胞、脾脏和肺中,而Fpr-rs3的RNA仅在骨骼肌中检测到。在任何测试组织中我们都未检测到Fpr-rs4或Fpr-rs5的RNA。此外,Fpr-rs5在对应于跨膜结构域VI的蛋白质编码区域有一个终止密码子,可能不编码功能性受体。这些结果表明,FPR基因簇在哺乳动物中经历了差异性扩增,FPRL2、Fpr-rs2、Fpr-rs3、Fpr-rs4和Fpr-rs5是在人类和小鼠分化后产生的。

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