Chd8 haploinsufficiency impacts rearing experience in C57BL/6 mice

Area of Science:

• Neurodevelopmental disorders
• Genetics
• Animal models

Background:

• Mutations in CHD8 (Chromodomain helicase DNA binding protein 8) are a significant genetic risk factor for autism spectrum disorder (ASD).
• Mouse models of Chd8 haploinsufficiency exhibit ASD-related phenotypes, but results vary, suggesting potential confounding factors.
• Altered maternal care is a potential source of variation in Chd8 mouse models, though not directly studied.

Purpose of the Study:

• To investigate the impact of Chd8 haploinsufficiency in offspring on maternal behavior.
• To examine the effects of maternal Chd8 haploinsufficiency on pup care and survival.
• To understand how Chd8 genotype influences early-life maternal-offspring interactions in mice.

Main Methods:

• Systematic observation of maternal care in C57BL/6 mice.
• Comparison of maternal behaviors towards litters with wild-type (WT) and Chd8-heterozygous offspring.
• Assessment of maternal care by WT dams and Chd8-heterozygous dams.

Main Results:

• Wild-type dams showed reduced maternal behaviors towards mixed-genotype litters compared to WT litters, especially in the first postnatal week.
• Maternal Chd8 haploinsufficiency led to decreased litter survival and increased active maternal care.
• These effects were most pronounced during the first postnatal week.

Conclusions:

• Chd8 haploinsufficiency in either offspring or dams significantly impacts maternal care and litter survival in mice.
• Early-life experiences, including maternal interactions, are influenced by Chd8 genotype.
• Understanding these effects is crucial for interpreting Chd8 mouse model phenotypes and ASD mechanisms.