A CONSTITUTIVELY ACTIVE MUTANT PTH-PTHRP RECEPTOR IN JANSEN-TYPE METAPHYSEAL CHONDRODYSPLASIA
A CONSTITUTIVELY ACTIVE MUTANT PTH-PTHRP RECEPTOR IN JANSEN-TYPE METAPHYSEAL CHONDRODYSPLASIA
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DOI：
10.1126/science.7701349
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发表时间：
1995-04-07
期刊：
影响因子：
56.9
通讯作者：
JUPPNER, H
中科院分区：
文献类型：
--
作者：
SCHIPANI, E;KRUSE, K;JUPPNER, H
在1例Jansen型干骺端软骨发育不良患者中发现了甲状旁腺激素-甲状旁腺激素相关肽(PTH-PTHrP)受体基因外显子M2的单一杂合性核苷酸交换，它将受体第一细胞内环中223位严格保守的组氨酸残基改变为精氨酸。在表达突变型PTH-PTHrP受体的COS-7细胞中观察到结构性的、非配体依赖的腺苷3‘，5’-单磷酸蓄积，而在表达野生型受体的细胞中则没有。这一发现解释了这种罕见的短肢侏儒症中严重的非配体依赖型高钙血症和低磷血症，以及最可能的软骨内骨的异常形成。
A single heterozygous nucleotide exchange in exon M2 of the gene encoding the parathyroid hormone-parathyroid hormone-related peptide (PTH-PTHrP) receptor was identified in a patient with Jansen-type metaphyseal chondrodysplasia, which changes a strictly conserved histidine residue at position 223 in the receptor's first intracellular loop to arginine. Constitutive, ligand-independent adenosine 3',5'-monophosphate accumulation was observed in COS-7 cells expressing the mutant PTH-PTHrP receptor but not in cells expressing the wild-type receptor. This finding explains the severe ligand-independent hypercalcemia and hypophosphatemia, and most likely the abnormal formation of endochondral bone, in this rare form of short-limbed dwarfism.