Gene by environment interaction mouse model reveals a functional role for 5-hydroxymethylcytosine in neurodevelopmental disorders.

ABSTRACT: Mouse knockouts of Cntnap2 show altered neurodevelopmental behavior, deficits in striatal GABAergic signaling, and a genome-wide disruption of an environmentally sensitive DNA methylation modification (5-hydroxymethylcytosine [5hmC]) in the orthologs of a significant number of genes implicated in human neurodevelopmental disorders. We tested adult Cntnap2 heterozygous mice (Cntnap2 ^+/-; lacking behavioral or neuropathological abnormalities) subjected to a prenatal stress and found that prenatally stressed Cntnap2 ^+/- female mice show repetitive behaviors and altered sociability, similar to the homozygote phenotype. Genomic profiling revealed disruptions in hippocampal and striatal 5hmC levels that are correlated to altered transcript levels

SUBMITTER: Papale LA 

PROVIDER: S-EPMC8805724 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature