한빛사 논문
National Institutes of Health, University of Maryland School of Medicine
Yuyoung Joo1, Yutong Xue1, Yue Wang2, Ross A. McDevitt3, Nirnath Sah2, Simone Bossi1, Shuaikun Su1, Seung Kyu Lee1, Wei Peng1, Aoji Xie1, Yongqing Zhang1, Yi Ding4, Wai Lim Ku4, Soumita Ghosh5, Kenneth Fishbein5, Weiping Shen1, Richard Spencer5, Kevin Becker1, Keji Zhao4, Mark P. Mattson2, Henriette van Praag2,6, Alexei Sharov1,* & Weidong Wang1,*
1 Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. 2 Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. 3 The Comparative Medicine Section, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. 4 Laboratory of Epigenome Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. 5 Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. 6 Present address: Brain Institute and Charles E. Schmidt College of Medicine, Jupiter, FL 33458, USA.
*Corresponding author
Abstract
Topoisomerase 3β (Top3β) is the only dual-activity topoisomerase in animals that can change topology for both DNA and RNA, and facilitate transcription on DNA and translation on mRNAs. Top3β mutations have been linked to schizophrenia, autism, epilepsy, and cognitive impairment. Here we show that Top3β knockout mice exhibit behavioural phenotypes related to psychiatric disorders and cognitive impairment. The mice also display impairments in hippocampal neurogenesis and synaptic plasticity. Notably, the brains of the mutant mice exhibit impaired global neuronal activity-dependent transcription in response to fear conditioning stress, and the affected genes include many with known neuronal functions. Our data suggest that Top3β is essential for normal brain function, and that defective neuronal activity-dependent transcription may be a mechanism by which Top3β deletion causes cognitive impairment and psychiatric disorders.
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