Topoisomerase 3β knockout mice show transcriptional and behavioural impairments associated with neurogenesis and synaptic plasticity.
Yuyoung JooYutong XueYue WangRoss A McDevittNirnath SahSimone BossiShuaikun SuSeung Kyu LeeWei PengAoji XieYongqing ZhangYi DingWai Lim KuSoumita GhoshKenneth FishbeinWeiping ShenRichard SpencerKevin BeckerKeji ZhaoMark P MattsonHenriette van PraagAlexei SharovWeidong WangPublished in: Nature communications (2020)
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.
Keyphrases
- cognitive impairment
- cerebral ischemia
- transcription factor
- subarachnoid hemorrhage
- circulating tumor
- brain injury
- single molecule
- high fat diet induced
- blood brain barrier
- autism spectrum disorder
- bipolar disorder
- gene expression
- white matter
- nucleic acid
- wild type
- genome wide
- adipose tissue
- oxidative stress
- resting state
- functional connectivity
- machine learning
- big data
- dna methylation
- insulin resistance
- deep learning
- electronic health record
- circulating tumor cells
- heat stress
- artificial intelligence
- genome wide identification
- dna binding