Parathyroid hormone-related protein is a developmental regulatory molecule.
Parathyroid hormone-related protein is a developmental regulatory molecule.
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DOI：
10.1111/j.1600-0722.1998.tb02150.x
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发表时间：
1998
影响因子：
1.9
通讯作者：
W. Philbrick
中科院分区：
文献类型：
--
作者：
W. Philbrick
甲状旁腺激素相关肽(PTHrP)被发现是恶性肿瘤体液高钙综合征的主要致病物质。现在已经知道，PTHrP和PTH基因是在一个古老的复制事件的基础上产生的。这一遗传的一个结果是每个肽的N-末端有一段高度同源的短序列，另一个事实是这些N-末端产物似乎由单个G蛋白偶联受体服务，称为I型受体。最近，小鼠的过表达和无效策略提供了令人信服的证据，表明PTHrP的功能之一是作为发育调节分子。例如，PTHrP在角质形成细胞、乳腺上皮细胞和软骨细胞中的过度表达导致每个病例的发育表型，而该基因的敲除与出生时致命的软骨营养不良有关。通过一种遗传策略拯救PTHrP缺失的小鼠，该策略涉及到在软骨细胞中靶向过表达PTHrP的转基因小鼠和敲除小鼠之间的杂交，提供了一个窗口，揭示了在具有共同的上皮-间充质形态发生背景的多个组织中先前未被认识的PTHrP发育调节作用。
Parathyroid hormone-related peptide (PTHrP) was discovered as the tumor product that is responsible for most instances of the syndrome of humoral hypercalcemia of malignancy. It is now known that the PTHrP and PTH genes arose on the basis of an ancient duplication event. One result of this heritage is a short stretch of highly homologous sequence at the N-terminus of each of the peptides, and another is the fact that these N-terminal products seem to be serviced by a single G protein-coupled receptor referred to as the type I receptor. Overexpression and null strategies in mice have recently provided convincing evidence that one such PTHrP function is as a developmental regulatory molecule. For example, overexpression of PTHrP in keratinocytes, mammary epithelial cells and chondrocytes results in a developmental phenotype in each case, while knockout of the gene is associated with a chondrodystrophy that is lethal at birth. Rescue of the PTHrP-null mouse via a genetic strategy involving a cross between the knockout mouse and a transgenic mouse with targeted PTHrP overexpression in chondrocytes provides a window on previously unappreciated PTHrP developmental regulatory effects in multiple tissues that share a common epithelial-mesenchymal morphogenetic background.