DNA methylation analysis of tissue specificity and chronological changes in mouse model of human child abuse

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K21124
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0908:Society medicine, nursing, and related fields
• Research Institution: Nihon University
• Principal Investigator: OKANO Masaharu 日本大学, 歯学部, 助教 (70906544)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: マウス母子分離実験 / DNAメチル化 / MS-HRM法 / 児童虐待

Outline of Final Research Achievements

Recent studies have reported altered DNA methylation in several human genes in neuropsychiatric disorders associated with child abuse, suggesting that DNA methylation is a biomarker candidate to estimate child abuse. Maternal separation (MS) in mice is an excellent experimental model to elucidate the relationship between stress in child neglect and DNA methylation status. In this study, we analyzed methylation levels (Df values) of 3 genes associated with child abuse and neuropsychiatric disorders. Litter mates were exposed to MS for 2 hours over 14 consecutive days (MS group), or left undisturbed (control group). Methylation status of genomic DNA extracted from amygdala of mice in both groups were measured using MS-HRM method. Df value of Myt1l gene in the MS group (-25.3 ± 0.4) was significantly higher than that in the control group (-26.7 ± 0.1, p < 0.05). MS-dependent change of CpG methylation in Myt1l is useful as a biomarker for experienced child abuse.

Free Research Field

法医学

Academic Significance and Societal Importance of the Research Achievements

虐待被害の有無は，被虐待者の訴えや身体所見から判断されており，客観的な評価は難しいため，虐待被害の新たな指標が社会的に求められている。また，マウスの母子分離処置は，児童虐待ストレスとメチル化変化との連関を検証するために有用な実験モデルである。Myt1lなどの一部の遺伝子におけるCpG配列のメチル化は，ヒトの虐待被害とマウスの母子分離ストレスとの間で共通することが示唆された。DNAメチル化率の変化に基づいたヒトにおけるネグレクト被害の存否を示す分子生物学的な指標の開発のために，マウスを用いた母子分離実験によるストレスの曝露量とDNAメチル化の変化量との関連性解明へつながる研究成果が得られた。