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2021 Fiscal Year Final Research Report

Corepressor Regulation of Thyroid Hormone Action in central nervous system

Research Project

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Project/Area Number 19K16486
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 48020:Physiology-related
Research InstitutionGunma University

Principal Investigator

Amano Izuki  群馬大学, 大学院医学系研究科, 講師 (10765275)

Project Period (FY) 2019-04-01 – 2022-03-31
Keywords抑制型転写共役因子 / 脳発達 / 甲状腺ホルモン / NCoR1 / SMRT / 自閉症スペクトラム障害
Outline of Final Research Achievements

NCoR1 and SMRT are critical coregulators of the thyroid hormone receptor (TR), mediating transcriptional repression via histone deacetylation. How the corepressors regulate TR signaling is not fully understood, especially in central nervous system. To determine the role of NCoR1 and SMRT in the CNS, we used mice with neuronal specific NCoR1/SMRT knock-out mice. We found that neuronal specific NCoR1 or SMRT knock-out mice survive without obvious impairment of neuronal development. However, NCoR1/SMRT double knock-out mice die within postnatal 1-2 weeks and have impaired body growth. In addition, adult single NCoR1/SMRT knock-out mice showed impaired social functioning and emotion similar to some autism spectrum disorder (ASD) symptoms. Thus, both NCoR1/SMRT have important roles in maintaining normal neuronal function. Also, these mice have potentials to reveal the mechanism of ASD.

Free Research Field

内分泌生理

Academic Significance and Societal Importance of the Research Achievements

本研究は、抑制型転写共役因子であるNCoR1/SMRTの中枢神経系における役割をマウスモデルを用いて明らかにするものである。近年、NCoRsの遺伝子異常が自閉症スペクトラム障害の原因であることを示唆する症例が報告されており、その社会的ニーズは大きい。本研究では神経細胞特異的にNCoR1/SMRTを欠損するマウスを作出した。その結果、遺伝子改変動物においても情動、社会性行動の異常や日内活動量の変化が観察されるなど、自閉症スペクトラム障害に類似した表現型を呈することを明らかにした。本モデルマウスが自閉症スペクトラム障害の解明の一助になることが期待される。

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Published: 2023-01-30  

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