Chd8 haploinsufficiency impacts rearing experience in C57BL/6 mice,Genes, Brain and Behavior

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Chd8 haploinsufficiency impacts rearing experience in C57BL/6 mice
Genes, Brain and Behavior ( IF 2.4 ) Pub Date : 2024-04-01 , DOI: 10.1111/gbb.12892
Manal Tabbaa _{1,

2} , Pat Levitt _{1,

2}

Affiliation

Mutations in CHD8 are one of the highest genetic risk factors for autism spectrum disorder. Studies in mice that investigate underlying mechanisms have shown Chd8 haploinsufficient mice display some trait disruptions that mimic clinical phenotypes, although inconsistencies have been reported in some traits across different models on the same strain background. One source of variation across studies may be the impact of Chd8 haploinsufficiency on maternal‐offspring interactions. While differences in maternal care as a function of Chd8 genotype have not been studied directly, a previous study showed that pup survival was reduced when reared by Chd8 heterozygous dams compared with wild‐type (WT) dams, suggesting altered maternal care as a function of Chd8 genotype. Through systematic observation of the C57BL/6 strain, we first determined the impact of Chd8 haploinsufficiency in the offspring on WT maternal care frequencies across preweaning development. We next determined the impact of maternal Chd8 haploinsufficiency on pup care. Compared with litters with all WT offspring, WT dams exhibited less frequent maternal behaviors toward litters consisting of offspring with mixed Chd8 genotypes, particularly during postnatal week 1. Dam Chd8 haploinsufficiency decreased litter survival and increased active maternal care also during postnatal week 1. Determining the impact of Chd8 haploinsufficiency on early life experiences provides an important foundation for interpreting offspring outcomes and determining mechanisms that underlie heterogeneous phenotypes.

中文翻译：

Chd8 单倍体不足影响 C57BL/6 小鼠的饲养体验

CHD8 突变是自闭症谱系障碍的最高遗传风险因素之一。对研究潜在机制的小鼠研究表明，Chd8 单倍体不足小鼠表现出一些模拟临床表型的性状破坏，尽管在相同菌株背景下，不同模型的某些性状存在不一致。研究间差异的一个来源可能是 Chd8 单倍体不足对母系-后代相互作用的影响。虽然尚未直接研究作为 Chd8 基因型功能的母体护理差异，但先前的一项研究表明，与野生型（WT）母体相比，由 Chd8 杂合母体饲养的幼崽存活率降低，这表明母体护理作为 Chd8 基因型的功能发生了变化。通过对 C57BL/6 菌株的系统观察，我们首先确定了后代 Chd8 单倍体不足对断奶前发育过程中 WT 母体护理频率的影响。接下来，我们确定了母体 Chd8 单倍体不足对幼犬护理的影响。与所有 WT 后代的窝产仔数相比，WT 母体对由混合 Chd8 基因型的后代组成的窝产仔猪表现出较少的母体行为，尤其是在出生后第 1 周。Dam Chd8 单倍体不足降低了窝存活率，并在出生后第 1 周增加了积极的孕产妇护理。确定 Chd8 单倍体不足对早期生活经历的影响为解释后代结局和确定异质表型的基础机制提供了重要基础。

更新日期：2024-04-01

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