title: Loss of ZBTB20 impairs circadian output and leads to unimodal behavioral rhythms.
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 geneZbtb20plays a crucial role in the regulation of bimodal activities in mice. Depletion ofZbtb20in nerve system resulted in the loss of early evening activity, but the increase of morning activity. We found thatZbtb20-deficient mice exhibited a pronounced decrease in the expression ofProkr2and resembled phenotypes ofProk2andProkr2-knockout mice. Injection of adeno-associated virus-double-floxedProkr2in suprachiasmatic nucleus could partly restore evening activity inNestin-Cre; Zbtb20fl/fl(NS-ZB20KO) mice. Furthermore, loss ofZbtb20inFoxg1loci, 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.
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Qu
authors.affiliation: Department of Pathophysiology, Second Military Medical University, Shanghai, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Cambridge-Suda Genomic Research Center, Soochow University, Suzhou, China.
authors.forename: Moli
authors.initials: M
authors.lastname: Huang
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: Guangsen
authors.initials: G
authors.lastname: Shi
authors.affiliation: Cambridge-Suda Genomic Research Center, Soochow University, Suzhou, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Liu
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: Pancheng
authors.identifier: http://orcid.org/0000-0001-6311-6092
authors.initials: P
authors.lastname: Xie
authors.affiliation: Department of Pathophysiology, Second Military Medical University, Shanghai, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Cambridge-Suda Genomic Research Center, Soochow University, Suzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Xu
authors.affiliation: Cambridge-Suda Genomic Research Center, Soochow University, Suzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Cambridge-Suda Genomic Research Center, Soochow University, Suzhou, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Guocun
authors.initials: G
authors.lastname: Huang
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Joseph S
authors.identifier: http://orcid.org/0000-0003-0384-8878
authors.initials: JS
authors.lastname: Takahashi
authors.affiliation: Department of Pathophysiology, Second Military Medical University, Shanghai, China.
authors.forename: Weiping J
authors.identifier: http://orcid.org/0000-0003-4727-2380
authors.initials: WJ
authors.lastname: Zhang
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, China.|Cambridge-Suda Genomic Research Center, Soochow University, Suzhou, China.
authors.forename: Ying
authors.identifier: http://orcid.org/0000-0002-6689-7768
authors.initials: Y
authors.lastname: Xu
keywords: PROKR2; ZBTB20; behavior rhythms; circadian output gene; locomotor; mouse; neurodegenerative disorders; neuroscience