Skeletal abnormalities in Pth-null mice are influenced by dietary calcium
Skeletal abnormalities in Pth-null mice are influenced by dietary calcium
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DOI：
10.1210/en.2003-1097
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发表时间：
2004-04-01
期刊：
影响因子：
4.8
通讯作者：
Karaplis, AC
中科院分区：
文献类型：
--
作者：
Miao, DS;He, B;Karaplis, AC
我们已经研究了PTH在出生后状态中的作用，在PTH缺乏症的小鼠模型中，通过靶向胚胎干细胞中的PTH基因产生。当维持正常钙摄入量时，消融等位基因纯合子小鼠发生低钙血症、高磷血症和低循环1，25-二羟维生素D-3 [1，25（OH）（2）D-3]水平，与原发性甲状旁腺功能减退一致。骨转换减少，导致PTH缺陷小鼠的骨小梁和皮质骨体积增加。当将突变小鼠置于低钙饮食中时，尽管没有PTH，但肾脏25-羟基维生素D 1 α-羟化酶表达增加，导致循环1，25（OH）（2）D-3水平升高，显着的破骨细胞生成和严重的骨吸收。这些研究证明了PTH基因耗竭动物的骨骼表型依赖于外部环境以及内部激素和离子循环因子。他们还表明，虽然PTH作用是对低钙血症的第一防御，但即使在没有PTH的情况下，1，25（OH）（2）D-3也可以被动员，以防止极度缺钙。
We have examined the role of PTH in the postnatal state in a mouse model of PTH deficiency generated by targeting the Pth gene in embryonic stem cells. Mice homozygous for the ablated allele, when maintained on a normal calcium intake, developed hypocalcemia, hyperphosphatemia, and low circulating 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] levels consistent with primary hypoparathyroidism. Bone turnover was reduced, leading to increased trabecular and cortical bone volume in PTH-deficient mice. When mutant mice were placed on a low-calcium diet, renal 25-hydroxyvitamin D 1 alpha-hydroxylase expression increased despite the absence of PTH, leading to a rise in circulating 1,25(OH)(2)D-3 levels, marked osteoclastogenesis, and profound bone resorption. These studies demonstrate the dependence of the skeletal phenotype in animals with genetically depleted PTH on the external environment as well as on internal hormonal and ionic circulatory factors. They also show that, although PTH action is the first defense against hypocalcemia, 1,25(OH)(2)D-3 can be mobilized, even in the absence of PTH, to guard against extreme calcium deficiency.