Characterization of mice deficient in Melanocortin 2 receptor on a B6/Balbc mix background

Characterization of mice deficient in Melanocortin 2 receptor on a B6/Balbc mix background
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DOI:
10.1016/j.mce.2008.10.027
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发表时间:
2009-03-05
影响因子:
4.1
通讯作者:
Iwakura, Yoichiro
Iwakura, Yoichiro
中科院分区:
医学2区
文献类型:
--
作者:
Chida, Dai;Sato, Tsuyoshi;Iwakura, Yoichiro

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我们以前曾报道,黑皮质素2受体(MC 2 R(-/-))缺陷的小鼠B6 N5代表现出肉眼可检测的肾上腺明显萎缩的束状核(zF)和缺乏可检测水平的皮质酮,并降低血清中的醛固酮和肾上腺素浓度。所有B6/N8背景的MC 2 R(-/-)小鼠在出生后2天内死亡,而B6/Balbc混合背景的MC 2 R(-/-)小鼠中约有一半存活至成年。雄性和雌性MC 2 R(-/-)小鼠均具有生育能力,表明生殖器官发育和功能正常。从MC 2 R(-/-)母鼠分娩的MC 2 R(-/-)小鼠由于肺衰竭而未能存活,这表明胎儿或母体皮质酮对肺成熟至关重要。MC 2 R(-/-)小鼠对免疫和非免疫刺激均不能激活下丘脑-垂体-肾上腺轴。MC 2 R(-/-)小鼠在低醛固酮和不可检测水平的皮质酮下通过激活肾素-血管紧张素-醛固酮系统维持肾小球结构并实现电解质稳态。(C)2008爱思唯尔爱尔兰有限公司保留所有权利。
We have previously reported that Melanocortin 2 receptor (MC2R(-/-)) deficient mice on B6 N5 generations exhibited macroscopically detectable adrenal glands with markedly atrophied zona fasciculata (zF) and lack of detectable levels of corticosterone, and reduced serum concentrations of aldosterone and epinephrine. All MC2R(-/-) mice on B6/N8 background die within 2 days after birth, while about half of the MC2R(-/-) mice on B6/Balbc mix background survived to adulthood. Both male and female MC2R(-/-) mice were fertile, suggesting that normal development and function of reproductive organs. MC2R(-/-) mice delivered from MC2R(-/-) dams failed to survive due to lung failure, suggesting that fetal or maternal corticosterone is essential for lung maturation. MC2R(-/-) mice failed to activate the hypothalamic-pituitary-adrenal axis in response to both immune and non-immune stimuli. MC2R(-/-) mice maintained glomerular structure and achieved electrolyte homeostasis by the activation of the renin-angiotensin-aldosterone system under low aldosterone and undetectable levels of corticosterone. (C) 2008 Elsevier Ireland Ltd. All rights reserved.