Chd8 haploinsufficiency impairs early brain development and protein homeostasis later in life.

ABSTRACT:

Background

Chromodomain helicase DNA-binding protein 8 (Chd8) is a high-confidence risk gene for autism spectrum disorder (ASD). However, how Chd8 haploinsufficiency impairs gene expression in the brain and impacts behavior at different stages of life is unknown.

Methods

We generated a mutant mouse line with an ASD-linked loss-of-function mutation in Chd8 (V986*; stop codon mutation). We examined the behavior of Chd8 mutant mice along with transcriptional changes in the cerebral cortex as a function of age, with a focus on one embryonic (E14.5) and three postnatal ages (1, 6, and 12 months).

Results

Chd8^V986*/+ mutant mice displayed macrocephaly, reduced rearing responses and reduced center time in the open field, and enhanced social novelty preference. Beh

SUBMITTER: Jimenez JA 

PROVIDER: S-EPMC7537101 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature