PLX109742

GSE145730: Topoisomerase 3bis essential for neuronal activity-dependent transcription, neurogenesis, and synaptic and behavioral neuroplasticity

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

Topoisomerase 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. SOURCE: Weidong Wang (wangw@grc.nia.nih.gov) - Lab of Genetics and Genomics National Institute on Aging/NIH