Loss of ZBTB20 impairs circadian output and leads to unimodal behavioral rhythms

Loss of ZBTB20 impairs circadian output and leads to unimodal behavioral rhythms
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ZBTB20 的缺失会损害昼夜节律输出并导致单峰行为节律

DOI:
10.7554/elife.17171
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发表时间:
2016-09-22
期刊:
影响因子:
7.7
通讯作者:
Xu, Ying
Xu, Ying
中科院分区:
生物学1区
文献类型:
--
作者:
Qu, Zhipeng;Zhang, Hai;Xu, Ying

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许多动物在白天/夜晚周期中表现出早晨和晚上的双峰活动。然而,很少有人知道有关的潜在成分参与调节哺乳动物的双峰行为节律。在这里,我们确定了锌指蛋白基因Zbtb 20在调节小鼠的双峰活动中起着至关重要的作用。Zbtb 20在神经系统中的消耗导致了早夜活动的丧失,但早晨活动增加。我们发现Zbtb 20缺陷小鼠表现出Prokr 2表达的显著降低,并且与Prok 2和Prokr 2敲除小鼠的表型相似。在视交叉上核内注射腺相关病毒-双floxed Prokr 2可部分恢复Nestin-Cre; Zbtb 20 fl/fl(NS-ZB 20 KO)小鼠的夜间活动。此外,Zbtb 20在Foxg 1基因座中的丢失,但在视交叉上核中的完整性,不是NS-ZB 20 KO小鼠的单峰活动的原因。我们的研究提供了ZBTB 20介导的PROKR 2信号传导对夜间行为节律至关重要的证据。DOI:http://dx.doi.org/10.7554/eLife.17171.001网站
Many animals display morning and evening bimodal activities in the day/night cycle. However, little is known regarding the potential components involved in the regulation of bimodal behavioral rhythms in mammals. Here, we identified that the zinc finger protein gene Zbtb20 plays a crucial role in the regulation of bimodal activities in mice. Depletion of Zbtb20 in nerve system resulted in the loss of early evening activity, but the increase of morning activity. We found that Zbtb20-deficient mice exhibited a pronounced decrease in the expression of Prokr2 and resembled phenotypes of Prok2 and Prokr2-knockout mice. Injection of adeno-associated virus-double-floxed Prokr2 in suprachiasmatic nucleus could partly restore evening activity in Nestin-Cre; Zbtb20fl/fl (NS-ZB20KO) mice. Furthermore, loss of Zbtb20 in Foxg1 loci, but intact in the suprachiasmatic nucleus, was not responsible for the unimodal activity of NS-ZB20KO mice. Our study provides evidence that ZBTB20-mediated PROKR2 signaling is critical for the evening behavioral rhythms. DOI: http://dx.doi.org/10.7554/eLife.17171.001