期刊
NATURE NEUROSCIENCE
卷 21, 期 12, 页码 1689-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41593-018-0261-7
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资金
- National Key R&D Program of China [2018YFA0108001]
- Natural Science Foundation of China [31590831, 91640204, 81571212]
- Strategic Priority Research Program of Chinese Academy of Science [XDB 19000000]
- National Institutes of Health [NS051630, NS079625, MH102690, AG047928]
- Simons Foundation Autism Research Initiative [239320]
- Hundred Talents Program of Chinese Academy of Science
- NARSAD Independent Investigator Award-Suzanne and John Golden Investigator sponsorship
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH102690] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS079625, R01NS051630] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [R01AG047928] Funding Source: NIH RePORTER
Genetic analyses have linked microRNA-137 (MIR137) to neuropsychiatric disorders, including schizophrenia and autism spectrum disorder. miR-137 plays important roles in neurogenesis and neuronal maturation, but the impact of miR-137 loss-of-function in vivo remains unclear. Here we show the complete loss of miR-137 in the mouse germline knockout or nervous system knockout (cKO) leads to postnatal lethality, while heterozygous germline knockout and cKO mice remain viable. Partial loss of miR-137 in heterozygous cKO mice results in dysregulated synaptic plasticity, repetitive behavior, and impaired learning and social behavior. Transcriptomic and proteomic analyses revealed that the miR-137 mRNA target, phosphodiesterase 10a (Pde10a), is elevated in heterozygous knockout mice. Treatment with the Pde10a inhibitor papaverine or knockdown of Pde10a ameliorates the deficits observed in the heterozygous cKO mice. Collectively, our results suggest that MIR137 plays essential roles in postnatal neurodevelopment and that dysregulation of miR-137 potentially contributes to neuropsychiatric disorders in humans.
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