Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan.
Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
FASEB J. 2022 Mar;36(3):e22232. doi: 10.1096/fj.202101624R.
Hybrid species have more genetic diversity than their parents. However, the impact of the hybrid genome of reciprocal crosses on brain function remains largely unknown. We performed behavioral, molecular, and neuronal analyses on C57BL/6J mice (B6), CAST/EiJ mice (CAST), and hybrid mice resulting from reciprocal crosses of the two strains, B6/CAST F1i and B6/CAST F1r, respectively. Hybrid mice displayed greater motor strength and coordination, food grinding, social dominance, and less sociability compared to their parental strains. Parental origin influenced body weight, locomotor speed, and heat nociception of hybrid mice. Parental origin, cell type, and the interaction of both affected expression patterns of hybrid genomes including imprinted genes. There was a correlation between affected genes and corresponding behavioral phenotypes. Hybrid genomes mediated neuronal activity in the locus coeruleus, a brain region implicated in arousal, adaptive behaviors, and sleep-wake cycle due to its norepinephrine projections throughout the central nervous system. The comprehensive brain phenotypes in these hybrid mice reveal important functional readouts associated with interactions of hybrid genomes and impacts of parental genomes.
杂种比其亲本具有更多的遗传多样性。然而，正反交杂种基因组对大脑功能的影响在很大程度上仍然未知。我们对 C57BL/6J 小鼠（B6）、CAST/EiJ 小鼠（CAST）以及分别由这两个品系正反交产生的杂种小鼠 B6/CAST F1i 和 B6/CAST F1r 进行了行为、分子和神经元分析。与亲本品系相比，杂种小鼠表现出更强的运动力量和协调性、食物研磨、社会支配地位以及较低的社交能力。亲本来源影响杂种小鼠的体重、运动速度和热痛觉。亲本来源、细胞类型以及两者的相互作用影响包括印记基因在内的杂种基因组的表达模式。受影响的基因与相应的行为表型之间存在相关性。杂种基因组介导蓝斑核中的神经元活动，蓝斑核是一个与觉醒、适应性行为和睡眠-觉醒周期相关的脑区，因为其去甲肾上腺素投射到中枢神经系统的各个部位。这些杂种小鼠的综合脑表型揭示了与杂种基因组相互作用和亲本基因组影响相关的重要功能结果。
