Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine, United States of America.
Department of Medicine, Tufts University School of Medicine, Boston, MA, United States of America.
PLoS One. 2022 Jul 22;17(7):e0271913. doi: 10.1371/journal.pone.0271913. eCollection 2022.
Mesoderm specific transcript (Mest)/paternally expressed gene-1 (Peg1) is an imprinted gene expressed predominantly from the paternal allele. Aberrations in maternal behavior were previously reported in a Mest global knockout mouse (Mesttm1Masu). In this study, we performed in-depth social and maternal behavioral testing in a mouse model of Mest inactivation developed in our laboratory (Mesttm1.2Rkz). Mice with paternal allele inactivation (MestpKO) did not show anxiety after testing in the elevated plus maze, open field trial, and marble burying; nor depression-like behaviors in the tail suspension test. MestpKO showed normal social behaviors and memory/cognition in the three-chamber box test and the novel object recognition test, respectively. Primiparous MestpKO and MestgKO (biallelic Mest inactivation) female mice exhibited normal nest building and maternal behavior; and, virgin MestpKO and MestgKO female mice showed normal maternal instinct. Analyses of gene expression in adult hypothalamus, embryonic day 14.5 whole brain and adult whole brain demonstrated full abrogation of Mest mRNA in MestpKO and MestgKO mice with no effect on miR-335 expression. Our data indicates no discernible impairments in object recognition memory, social behavior or maternal behavior resulting from loss of Mest. The basis for the differences in maternal phenotypic behaviors between Mesttm1Masu and Mesttm1.2Rkz is not known.
中胚层特异性转录因子(Mest)/父系表达基因 1(Peg1)是一种印记基因,主要从父本等位基因表达。先前在 Mest 全局敲除小鼠(Mesttm1Masu)中报道了母体行为异常。在本研究中,我们在本实验室开发的 Mest 失活小鼠模型(Mesttm1.2Rkz)中进行了深入的社交和母性行为测试。父本等位基因失活的小鼠(MestpKO)在高架十字迷宫、旷场试验和大理石掩埋试验中没有表现出焦虑;在悬尾试验中也没有表现出抑郁样行为。MestpKO 在三箱测试和新物体识别测试中分别表现出正常的社交行为和记忆/认知。初产 MestpKO 和 MestgKO(双等位基因 Mest 失活)雌性小鼠表现出正常的筑巢和母性行为;而处女 MestpKO 和 MestgKO 雌性小鼠表现出正常的母性本能。成年下丘脑、胚胎 14.5 天全脑和成年全脑的基因表达分析表明,MestpKO 和 MestgKO 小鼠中的 Mest mRNA 完全被阻断,而 miR-335 的表达不受影响。我们的数据表明,Mest 缺失不会导致物体识别记忆、社交行为或母性行为明显受损。Mesttm1Masu 和 Mesttm1.2Rkz 之间母体表型行为差异的基础尚不清楚。