Calvi L M, Schipani E
Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
J Endocrinol Invest. 2000 Sep;23(8):545-54. doi: 10.1007/BF03343773.
JMC is a rare autosomal dominant form of short limb dwarfism characterized by asymptomatic hypercalcemia and skeletal deformities, despite low PTH and PTHrP levels. This rare disorder is likely to be caused by activating mutations in the PTH/PTHrP receptor leading to ligand-independent cAMP accumulation. The analysis of genetically altered mice which lack either PTHrP or the PTH/PTHrP receptor, as well as of transgenic mice in which the mutant receptor is targeted to the growth plate, has provided a molecular explanation for the severe skeletal abnormalities seen in JMC. In addition, the study of this rare human disorder has further elucidated the fundamental role played by the PTH/PTHrP receptor in mediating both the paracrine/autocrine actions of PTHrP in growth plate development and bone elongation, as well as the endocrine actions of PTH. The insight gained from the study of this human disease model is likely to continue to provide an important tool to define the cellular and molecular mechanisms that mediate the biological roles of the PTH, PTHrP and their receptor.
杰克逊-魏斯综合征（JMC）是一种罕见的常染色体显性短肢侏儒症，其特征是尽管甲状旁腺激素（PTH）和甲状旁腺激素相关蛋白（PTHrP）水平较低，但仍有无症状性高钙血症和骨骼畸形。这种罕见疾病可能是由PTH/PTHrP受体的激活突变导致非配体依赖性环磷酸腺苷（cAMP）积累引起的。对缺乏PTHrP或PTH/PTHrP受体的基因改变小鼠，以及突变受体靶向生长板的转基因小鼠的分析，为JMC中出现的严重骨骼异常提供了分子解释。此外，对这种罕见人类疾病的研究进一步阐明了PTH/PTHrP受体在介导PTHrP在生长板发育和骨骼伸长中的旁分泌/自分泌作用以及PTH的内分泌作用中所起的基本作用。从对这种人类疾病模型的研究中获得的见解可能会继续提供一个重要工具，以确定介导PTH、PTHrP及其受体生物学作用的细胞和分子机制。
