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of Genetics and Genomics, National Institute on Aging/NIHhttps://www.ebi.ac.uk/ena/browser/view/PRJNA608010Mus musculusxref:PubMed:32561719Topoisomerase 3b (Top3b) 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. Top3b mutation has been linked to schizophrenia, autism, epilepsy, and cognitive impairment. However, whether and how Top3b mutations are causal to these disorders remain unclear. Here we show that Top3b knockout mice exhibit behavioral phenotypes related to psychiatric disorders and cognitive impairment, including increased anxiety and fear, abnormal social interactions, impaired context discrimination, and defective spatial learning and memory. In addition, these mice display deficits in adult 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 that are critical for neuronal functions and mental health. Our data suggest that Top3b is essential for normal brain function in multiple domains, and defective neuronal activity-dependent transcription may be a mechanism by which Top3b deletion causes cognitive impairment and psychiatric disorders. Overall design: ChIP-seq and total RNA-seq of wildtype and Top3b KO mice in normal (non-fear) condition and fear condition to assay activity dependent transcription.ENASynaptic Prunings, Brain, Neuronal Remodeling, Neuronal Plasticities, swivelase activity, Arborizations, Activity, DNA topoisomerase IV activity, DNA topoisomerase type II activity, Neurite Prunings, Neural Plasticity, DNA topoisomerase I activity, topoisomerase II, Neuronal Arborization, Neuronal Prunings, Dendritic Remodeling, untwisting enzyme activity, Dendrite Pruning, deoxyribonucleic topoisomerase activity, Neuronal Network, Axonal, Neuronal Network Remodeling, DNA topoisomerase II, Dendritic Pruning, Neuroplasticity, DNA topoisomerase (ATP-hydrolysing), Neuronal Network Remodelings, Dendrite Arborization, Dendrite Prunings, Neuronal Remodelings, Neuroplasticities, Axon., Network Remodeling, Axonal Pruning, topoisomerase, Plasticities, deoxyribonucleate topoisomerase, Neurite Pruning, Arborization, relaxing enzyme activity, Neural, Synaptic, Neurite, Brain Plasticity, Prunings, DNA-gyrase activity, Remodeling, Dendritic, Axon Pruning, DNA topoisomerase II activity, Neurogeneses, DNA gyrase activity, Plasticity, Pruning, Dendritic Prunings, Synaptic Pruning, type I DNA topoisomerase activity, Neuronal Pruning, Synaptic Plasticities, Dendritic Arborizations, Synaptic Plasticity, nicking-closing enzyme activity, Axonal Prunings, Neuronal Arborizations, Axon, Dendrite Arborizations, Remodelings, bacterial transcription, Neuronal, type I topoisomerase activity, Axon Prunings, Dendrite, Brain Plasticities, Dendritic Remodelings, Dendritic Arborization, Neural Plasticities, type II DNA topoisomerase activity, omega-protein activity, transcription from bacterial-type RNA polymerase promoter, neural cell differentiation, General activity, Network RemodelingsSynaptic Prunings, Brain, Neuronal Remodeling, Neuronal Plasticities, swivelase activity, Arborizations, Activity, DNA topoisomerase IV activity, DNA topoisomerase type II activity, Neurite Prunings, Neural Plasticity, DNA topoisomerase I activity, topoisomerase II, Neuronal Arborization, Neuronal Prunings, Dendritic Remodeling, untwisting enzyme activity, Dendrite Pruning, deoxyribonucleic topoisomerase activity, Neuronal Network, Axonal, Neuronal Network Remodeling, DNA topoisomerase II, Dendritic Pruning, Neuroplasticity, DNA topoisomerase (ATP-hydrolysing), Neuronal Network Remodelings, Dendrite Arborization, Dendrite Prunings, Neuronal Remodelings, Neuroplasticities, Axon., Network Remodeling, Axonal Pruning, topoisomerase, Plasticities, deoxyribonucleate topoisomerase, Neurite Pruning, Arborization, relaxing enzyme activity, Neural, Synaptic, Neurite, Brain Plasticity, Prunings, DNA-gyrase activity, Remodeling, Dendritic, Axon Pruning, DNA topoisomerase II activity, Neurogeneses, DNA gyrase activity, Plasticity, Pruning, Dendritic Prunings, Synaptic Pruning, type I DNA topoisomerase activity, Neuronal Pruning, Synaptic Plasticities, Dendritic Arborizations, Synaptic Plasticity, nicking-closing enzyme activity, Axonal Prunings, Neuronal Arborizations, Axon, Dendrite Arborizations, Remodelings, bacterial transcription, Neuronal, type I topoisomerase activity, Axon Prunings, Dendrite, Brain Plasticities, Dendritic Remodelings, Dendritic Arborization, Neural Plasticities, type II DNA topoisomerase activity, omega-protein activity, transcription from bacterial-type RNA polymerase promoter, neural cell differentiation, General activity, Network RemodelingsfalseTopoisomerase 3b is essential for neuronal activity-dependent transcription, neurogenesis, and synaptic and behavioral neuroplasticityTopoisomerase 3b is essential for neuronal activity-dependent transcription, neurogenesis, and synaptic and behavioral neuroplasticity2025-09-242020-05-24PRJNA608010GSE1457301009032561719