1. Topoisomerase 3β knockout mice show transcriptional and behavioural impairments associated with neurogenesis and synaptic plasticity
- Author
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Wei Peng, Kenneth W. Fishbein, Mark P. Mattson, Yuyoung Joo, Alexei A. Sharov, Soumita Ghosh, Yongqing Zhang, Simone Bossi, Yi Ding, Henriette van Praag, Keji Zhao, Shuaikun Su, Kevin G. Becker, Weidong Wang, Yutong Xue, Seung Kyu Lee, Weiping Shen, Yue Wang, Aoji Xie, Ross A. McDevitt, Wai Lim Ku, Richard G. Spencer, and Nirnath Sah
- Subjects
Male ,0301 basic medicine ,Transcription, Genetic ,Neurogenesis ,Science ,General Physics and Astronomy ,Hippocampal formation ,Hippocampus ,Article ,General Biochemistry, Genetics and Molecular Biology ,Stereotaxic Techniques ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Transcription (biology) ,Animals ,Humans ,Cognitive Dysfunction ,Fear conditioning ,lcsh:Science ,Mice, Knockout ,Neurons ,Neuronal Plasticity ,Multidisciplinary ,Behavior, Animal ,biology ,Mental Disorders ,Topoisomerase ,General Chemistry ,Synaptic Potentials ,Autism spectrum disorders ,Magnetic Resonance Imaging ,Disease Models, Animal ,030104 developmental biology ,DNA Topoisomerases, Type I ,Stereotaxic technique ,Synaptic plasticity ,Knockout mouse ,Schizophrenia ,biology.protein ,Female ,lcsh:Q ,Behavior Observation Techniques ,Neuroscience ,030217 neurology & neurosurgery - 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., Topoisomerase 3β (Top3β) solves topological stress in DNA or RNA metabolism and its mutations are linked to mental disorders. Here, the authors describe transcriptional and behavioural impairments in Top3β-knockout mice and show that these are linked to impaired neurogenesis and synaptic plasticity.
- Published
- 2020