期刊
EXPERIMENTAL NEUROBIOLOGY
卷 31, 期 3, 页码 158-172出版社
KOREAN SOC BRAIN & NEURAL SCIENCE, KOREAN SOC NEURODEGENERATIVE DISEASE
DOI: 10.5607/en22016
关键词
Astrocyte; MAOB; GAB; Striatum; Cerebellum; Conditional knockout mouse
资金
- Institute for Basic Science (IBS), Center for Cognition and Sociality [IBS-R001-D2]
In this study, an astrocyte-specific MAOB conditional knockout mouse was generated, and it was found that astrocytic MAOB is a critical enzyme for the synthesis of GABA in astrocytes.
Monoamine oxidase B (MAOB) is a key enzyme for GABA production in astrocytes in several brain regions. To date, the role of astrocytic MAOB has been studied in MAOB null knockout (KO) mice, although MAOB is expressed throughout the body. Therefore, there has been a need for genetically engineered mice in which only astrocytic MAOB is targeted. Here, we generated an astrocyte-specific MAOB conditional KO (cKO) mouse line and characterized it in the cerebellar and striatal regions of the brain. Using the CRISPR-Cas9 gene-editing technique, we generated Maob floxed mice (B6-Maob(em1Cjl)/Ibs) which have floxed exons 2 and 3 of Maob with two loxP sites. By crossing these mice with hGFAP-CreER(T2), we obtained Maob floxed::hGFAP-CreER(T2) mice which have a property of tamoxifen-inducible ablation of Maob under the human GFAP (hGFAP) promoter. When we treated Maob floxed::hGFAP-CreER(T2) mice with tamoxifen for 5 consecutive days, MAOB and GABA immunoreactivity were significantly reduced in striatal astrocytes as well as in Bergmann glia and lamellar astrocytes in the cerebellum, compared to sunflower oil-injected control mice. Moreover, astrocyte-specific MAOB cKO led to a 74.6% reduction in tonic GABA currents from granule cells and a 76.8% reduction from medium spiny neurons. Our results validate that astrocytic MAOB is a critical enzyme for the synthesis of GABA in astrocytes. We propose that this new mouse line could be widely used in studies of various brain diseases to elucidate the pathological role of astrocytic MAOB in the future.
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