LETHAL SKELETAL DYSPLASIA FROM TARGETED DISRUPTION OF THE PARATHYROID HORMONE-RELATED PEPTIDE GENE
LETHAL SKELETAL DYSPLASIA FROM TARGETED DISRUPTION OF THE PARATHYROID HORMONE-RELATED PEPTIDE GENE
复制标题
DOI：
10.1101/gad.8.3.277
复制
发表时间：
1994-02-01
影响因子：
10.5
通讯作者：
MULLIGAN, RC
中科院分区：
文献类型：
--
作者：
KARAPLIS, AC;LUZ, A;MULLIGAN, RC
通过同源重组的方法在小鼠胚胎干细胞中破坏甲状旁腺素相关肽（PTHrP）基因，并将无效等位基因导入小鼠生殖系。PTHrP无效突变纯合子小鼠出生后死亡，可能是由于窒息，并表现出广泛的软骨内骨发育异常。组织学检查显示软骨细胞增殖减少，与软骨细胞的过早成熟和骨形成加速有关。对早期发育阶段的分析表明，软骨生长障碍先于软骨内骨形成异常。其他组织中无明显形态学异常。这些结果提供了直接的证据，暗示PTHrP在正常骨骼发育，并强调其在人类骨软骨发育不良的潜在参与。
The parathyroid hormone-related peptide (PTHrP) gene was disrupted in murine embryonic stem cells by homologous recombination, and the null allele was introduced into the mouse germ line. Mice homozygous for the PTHrP null mutation died postnatally, probably from asphyxia, and exhibited widespread abnormalities of endochondral bone development. Histological examination revealed a diminution of chondrocyte proliferation, associated with premature maturation of chondrocytes and accelerated bone formation. Analysis of earlier developmental stages revealed that disturbance in cartilage growth preceded abnormal endochondral bone formation. There were no morphological abnormalities apparent in other tissues. These results provide direct evidence implicating PTHrP in normal skeletal development and serve to emphasize its potential involvement in human osteochondrodysplasias.