No evidence for a bone phenotype in GPRC6A knockout mice under normal physiological conditions

No evidence for a bone phenotype in GPRC6A knockout mice under normal physiological conditions
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DOI:
10.1677/jme-08-0149
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发表时间:
2009-03-01
影响因子:
3.5
通讯作者:
Braeuner-Osborne, Hans
Braeuner-Osborne, Hans
中科院分区:
医学3区
文献类型:
--
作者:
Wellendorph, Petrine;Johansen, Lars Dan;Braeuner-Osborne, Hans

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GPRC 6A是一种七跨膜受体,通过广泛的L-α-氨基酸介导信号传导,通过二价阳离子Ca 2+和Mg 2+增强信号传导。GPRC 6A转录本在许多哺乳动物组织中被检测到,但该受体的生理作用迄今尚不清楚。与密切相关的钙敏感受体类似,GPRC 6A已被提出作为骨和其他组织中的Ca 2+和氨基酸的代谢传感器。在本研究中,我们产生了第一个GPRC 6A基因敲除小鼠,并研究了它们的表型,特别关注骨稳态。所产生的GPRC 6A敲除小鼠是存活的和可生育的,发育正常,并且与野生型同窝小鼠相比,体重没有显著差异。骨矿物质密度,组织形态计量学和骨代谢的评估表明,13周龄的基因敲除小鼠和野生型小鼠之间没有显着差异。总之,我们的数据不支持GPRC 6A在正常骨生理学中的作用。分子内分泌学杂志(2009)42,215-223
GPRC6A is a seven-transmembrane receptor mediating signaling by a wide range Of L-alpha-amino acids, a signaling augmented by the divalent cations Ca2+ and Mg2+. GPRC6A transcripts are detected in numerous mammalian tissues, but the physiological role of the receptor is thus far elusive. Analogously to the closely related calcium-sensing receptor, GPRC6A has been proposed to function as a metabolic sensor of Ca2+ and amino acids in bone and other tissues. In the present study, we have generated the first GPRC6A knockout mice and studied their phenotype with particular focus on bone homeostasis. The generated GPRC6A knockout mice are viable and fertile, develop normally, and exhibit no significant differences in body weight compared with wild-type littermates. Assessment of bone mineral density, histomorphometry, and bone metabolism demonstrated no significant differences between 13-week-old knockout and wild-type mice. In conclusion, our data do not support a role for GPRC6A in normal bone physiology. Journal of Molecular Endocrinology (2009) 42, 215-223