cDNA cloning of the murine Pex gene implicated in X-linked hypophosphatemia and evidence for expression in bone
cDNA cloning of the murine Pex gene implicated in X-linked hypophosphatemia and evidence for expression in bone
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DOI：
10.1006/geno.1996.0421
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发表时间：
1996-08-15
期刊：
影响因子：
4.4
通讯作者：
Ecarot, B
中科院分区：
文献类型：
--
作者：
Du, L;Desbarats, M;Ecarot, B
最近发现的人类PEX基因编码一种中性内肽酶，在X连锁低磷血症患者中发生突变。PEX编码区的3'端和5'端尚未克隆，也未鉴定该基因的组织表达。在这里，我们报告的小鼠Pex基因的完整开放阅读框架的分离和表征，并证明其在骨中的表达。小鼠Pex cDNA被预测为编码749个氨基酸的蛋白质，其与可用的人PEX序列具有95%的同一性，并且与膜结合金属内肽酶家族的成员具有显著的同源性。北方印迹分析显示，在正常小鼠的骨和培养的成骨细胞中有一个6.6 kb的转录本，而在Hyp小鼠（人类X连锁低磷酸盐血症的小鼠同源物）的样品中检测不到。然而，通过RT-PCR扩增，在Hyp骨中可检测到Pex转录物。特别令人感兴趣的是，来自大鼠切牙的cDNA克隆显示与Pex cDNA的5'端具有93%的序列同一性，这表明Pex可能在另一钙化组织（牙齿）中表达。骨和牙齿矿化受损和肾脏磷酸盐重吸收紊乱与Pex表达改变的相关性表明，Pex基因产物可能在这些过程中发挥关键作用。(C)出版社：Academic Press，Inc.
The recently identified human PEX gene apparently encodes for a neutral endopeptidase that is mutated in patients with X-linked hypophosphatemia. The 3' and 5' ends of the coding region of PEX have not been cloned, nor has the tissue expression of the gene been identified. Here we report the isolation and characterization of the complete open reading frame of the mouse Pex gene and the demonstration of its expression in bone. Mouse Pex cDNA is predicted to encode a protein of 749 amino acids with 95% identity to the available human PEX sequence and significant homology to members of the membrane-bound metalloendopeptidase family. Northern blot analysis revealed a 6.6-kb transcript in bone and in cultured osteoblasts from normal mice that was not detectable in samples from the Hyp mouse, the murine homolog of human X-linked hypophosphatemia. Pex transcripts were, however, detectable in Hyp bone by RT-PCR amplification, Of particular interest, a cDNA clone from rat incisor shows 93% sequence identity to the 5' end of Pex cDNA, suggesting that Pex may be expressed in another calcified tissue, the tooth. The association of impaired mineralization of bone and teeth and disturbed renal phosphate reabsorption with altered expression of Pex suggests that the Pex gene product may play a critical role in these processes. (C) 1996 Academic Press, Inc.