Deficiency of CHAMP1, a gene related to intellectual disability, causes impaired neuronal development and a mild behavioural phenotype

CHAMP1 is a gene associated with intellectual disability, which was originally identified as being involved in the maintenance of kinetochore-microtubule attachment. To explore the neuronal defects caused by CHAMP1 deficiency, we established mice that lack CHAMP1. Mice that are homozygous knockout for CHAMP1 were slightly smaller than wild-type mice and died soon after birth on pure C57BL/6J background. Although gross anatomical defects were not found in CHAMP1(-/-) mouse brains, mitotic cells were increased in the cerebral cortex. Neuronal differentiation was delayed in CHAMP1(-/-) neural stem cells in vitro, which was also suggested in vivo by CHAMP1 knockdown. In a behavioural test battery, adult CHAMP1 heterozygous knockout mice showed mild memory defects, altered social interaction, and depression-like behaviours. In transcriptomic analysis, genes related to neurotransmitter transport and neurodevelopmental disorder were downregulated in embryonic CHAMP1(-/-) brains. These results suggest that CHAMP1 plays a role in neuronal development, and CHAMP1-deficient mice resemble some aspects of individuals with CHAMP1 mutations. Nagai et al. report the first characterization of a knockout mouse of CHAMP1, a gene mutated in individuals with intellectual disability. CHAMP1 deficiency delayed neuronal development and CHAMP1 heterozygous knockout mice exhibited mild memory defects, altered social interaction, and depression-like behaviours, resembling some aspects of the human phenotype.