Topoisomerase 3? knockout mice show transcriptional and behavioural impairments associated with neurogenesis and synaptic plasticity.

ABSTRACT: Topoisomerase 3? (Top3?) 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. Top3? mutations have been linked to schizophrenia, autism, epilepsy, and cognitive impairment. Here we show that Top3? 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 Top3? is essential for normal brain function, and that defective neuronal activity-dependent transcription may be a mechanism by which Top3? deletion causes cognitive impairment and psychiatric disorders.

SUBMITTER: Joo Y 

PROVIDER: S-EPMC7305123 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature