MECP2 Duplication Causes Aberrant GABA Pathways, Circuits and Behaviors in Transgenic Monkeys: Neural Mappings to Patients with Autism.

ABSTRACT: MECP2 gain-of-function and loss-of-function in genetically engineered monkeys recapitulates typical phenotypes in patients with autism, yet where MECP2 mutation affects the monkey brain and whether/how it relates to autism pathology remain unknown. Here we report a combination of gene-circuit-behavior analyses including MECP2 coexpression network, locomotive and cognitive behaviors, and EEG and fMRI findings in 5 MECP2 overexpressed monkeys (Macaca fascicularis; 3 females) and 20 wild-type monkeys (Macaca fascicularis; 11 females). Whole-genome expression analysis revealed MECP2 coexpressed genes significantly enriched in GABA-related signaling pathways, whereby reduced β-synchronization within fronto-parieto-occipital networks was associated with abnormal locomotive behaviors. Meanwhile,

SUBMITTER: Cai DC 

PROVIDER: S-EPMC7204082 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature