期刊
INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE
卷 82, 期 2, 页码 168-179出版社
WILEY
DOI: 10.1002/jdn.10172
关键词
dopamine; heterozygous; parent-of-origin effect; rat; transgenerational inheritance
资金
- intramural ISS funds
Behavioral phenotypes of dopamine-transporter heterozygous (DAT-HET) rats vary among different epigenotypes, with significant transgenerational effects observed specifically in the second generation. The study demonstrates that the genotype of maternal grandmothers can lead to marked alterations in circadian activity and social preferences in the offspring.
Behavioral phenotype differs among epigenotypes of dopamine-transporter heterozygous (DAT-HET) rats. Epigenetic regulations act through transgenerational effects, referring to phenotypic variations emerging at second or third generation. To investigate transgenerational influences exerted by maternal grandmothers, we developed breeding schemes where only the genotype of maternal grandmothers varied. HET females, to serve as MAT vs. MIX mothers, were generated, respectively, from WT x KO = MAT and MAT x KO = MIX breeding, with KO males acting as grandfather. The HET experimental groups, generated from either MAT or MIX mothers, were called MIX-by-MAT and MIX2 (male-fathers KO; asset-M: wild/healthy-allele from dam) or SOT and SIX (male-fathers WT; asset-P: mutated-allele from dam). Thus, sequelae of first encounter between wild/healthy and mutated DAT alleles (in maternal-lineage) were compared at first- (MAT-dam, WT-grandmother) vs. at second- (MIX-dam, HET-grandmother) generation. We characterized, within these epigenotypes, (1) circadian home-cage activity and (2) preference for social stimuli. Marked alterations of circadian activity appeared in MIX-by-MAT HETs, offspring of MAT-dams, compared with MIX2 HET (offspring of MIX-dams); The latter, in turn, were undistinguishable from WT-controls. A clear-cut social preference by WT rats was expressed towards SIX compared with SOT stimulus rats, confirming that the latter elicited reduced social motivations. In conclusion, significant epigenetic modulations took place in DAT-HET rats, as a function of maternal grandmother's genotype.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据