Persistent cortical excitatory neuron dysregulation in adult <i>Chd8</i> haploinsufficient mice.

ABSTRACT: CHD8 mutations cause autism spectrum disorder, cognitive deficits, and macrocephaly. Chd8 ^+/- mouse models exhibit macrocephaly and transcriptional pathology, with inconsistent findings regarding neurogenesis, neuron function, and behavior. Via stereology and single nucleus transcriptomics (snRNA-seq), we found increased Chd8 ^+/- cortical volume was not explained by increase in neuron number. Differential expression (DE) was present across cortical cell types, with excitatory neurons exhibiting high DE burden and shared and subclass-specific DE signatures. Bulk RNA-seq DE of constitutive Chd8 ^+/- and conditional Camk2a-Cre Chd8 ^+/- mice identified shared transcriptional pathology. DE in synaptosomal versus nucle

SUBMITTER: Canales CP 

PROVIDER: S-EPMC12157415 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature