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

Qu, Zhipeng; Zhang, Hai; Huang, Moli; Shi, Guangsen; Liu, Zhiwei; Xie, Pancheng; Li, Hui; Wang, Wei et al. · Elife · 2016

basic_science · Level V

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Abstract

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 <i>Zbtb20</i> plays a crucial role in the regulation of bimodal activities in mice. Depletion of <i>Zbtb20</i> in nerve system resulted in the loss of early evening activity, but the increase of morning activity. We found that <i>Zbtb20</i>-deficient mice exhibited a pronounced decrease in the expression of <i>Prokr2</i> and resembled phenotypes of <i>Prok2</i> and <i>Prokr2</i>-knockout mice. Injection of adeno-associated virus-double-floxed <i>Prokr2</i> in suprachiasmatic nucleus could partly restore evening activity in <i>Nestin-Cre; Zbtb20</i><sup>fl/fl</sup> (NS-ZB20KO) mice. Furthermore, loss of <i>Zbtb20</i> in <i>Foxg1</i> 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.