The essential role of Mbd5 in the regulation of somatic growth and glucose homeostasis in mice.

The essential role of Mbd5 in the regulation of somatic growth and glucose homeostasis in mice.
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DOI:
10.1371/journal.pone.0047358
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Xu G
Xu G
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Du Y;Liu B;Guo F;Xu G;Ding Y;Liu Y;Sun X;Xu G

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甲基化CpG结合域蛋白5(Methyl-CpG binding domain protein 5,MBD 5)属于MBD家族蛋白,在转录调控和发育过程中发挥重要作用。MBD 5功能的重要性被最近的研究所强调,暗示它是参与人类2q23.1微缺失综合征的候选基因。为了研究Mbd 5的生理作用,我们产生了敲除小鼠。Mbd 5缺陷小鼠表现出生长迟缓、消瘦和断奶前致死。观察到的生长迟缓与Mbd 5基因敲除幼崽的GH/IGF-1轴受损相关。Mbd 5在脑中的条件性敲除导致与全身缺失相似的表型,表明Mbd 5在神经系统中起调节出生后生长的作用。此外,由于胰岛素信号传导增加,突变小鼠还显示出葡萄糖耐量增强和胰岛素敏感性升高,最终导致葡萄糖稳态紊乱和低血糖症。这些结果表明Mbd 5是小鼠出生后生长和维持葡萄糖稳态的重要因子。
Methyl-CpG binding domain protein 5 (MBD5) belongs to the MBD family proteins, which play central roles in transcriptional regulation and development. The significance of MBD5 function is highlighted by recent studies implicating it as a candidate gene involved in human 2q23.1 microdeletion syndrome. To investigate the physiological role of Mbd5, we generated knockout mice. The Mbd5-deficient mice showed growth retardation, wasting and pre-weaning lethality. The observed growth retardation was associated with the impairment of GH/IGF-1 axis in Mbd5-null pups. Conditional knockout of Mbd5 in the brain resulted in the similar phenotypes as whole body deletion, indicating that Mbd5 functions in the nervous system to regulate postnatal growth. Moreover, the mutant mice also displayed enhanced glucose tolerance and elevated insulin sensitivity as a result of increased insulin signaling, ultimately resulting in disturbed glucose homeostasis and hypoglycemia. These results indicate Mbd5 as an essential factor for mouse postnatal growth and maintenance of glucose homeostasis.
甲基-CPG结合结构域蛋白的比较研究。
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