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Cell Rep ; 42(3): 112243, 2023 03 28.
Article in English | MEDLINE | ID: mdl-36933215

ABSTRACT

Advancing from gene discovery in autism spectrum disorders (ASDs) to the identification of biologically relevant mechanisms remains a central challenge. Here, we perform parallel in vivo functional analysis of 10 ASD genes at the behavioral, structural, and circuit levels in zebrafish mutants, revealing both unique and overlapping effects of gene loss of function. Whole-brain mapping identifies the forebrain and cerebellum as the most significant contributors to brain size differences, while regions involved in sensory-motor control, particularly dopaminergic regions, are associated with altered baseline brain activity. Finally, we show a global increase in microglia resulting from ASD gene loss of function in select mutants, implicating neuroimmune dysfunction as a key pathway relevant to ASD biology.


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Animals , Autistic Disorder/genetics , Zebrafish/genetics , Brain , Autism Spectrum Disorder/genetics , Brain Mapping
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