CHAMP1 Gene’s Role in Neuronal Development Described19.09.2022
A research team led by two Tohoku University scientists says it has uncovered the role of CHAMP1 in neuronal development. The study (“Deficiency of CHAMP1, a gene related to intellectual disability, causes impaired neuronal development and a mild behavioral phenotype”) appears in Brain Communications.
“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,” the investigators wrote.
“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 behavioral test battery, adult CHAMP1 heterozygous-knockout mice showed mild memory defects, altered social interaction, and depression-like behaviors. 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.”
Kozo Tanaka, PhD, from the Institute of Development, Aging and Cancer, and Noriko Osumi, PhD, from the Graduate School of Medicine, and their group studied mice with the CHAMP1 gene knocked out, where one or both of the genes from the father and mother were inactivated. When both of the CHAMP1 genes were deleted, mice died soon after birth. And despite no apparent brain structure abnormalities, the researchers found that neural cell migration towards the brain surface was delayed, indicating a delay in neuronal development.
When a single CHAMP1 gene was lost, mice demonstrated slight memory defects, impaired social skills, and depression-like behavior. These mild behavioral problems resembled some aspects of individuals with CHAMP1 mutations.
While many genes are related to intellectual disability, CHAMP1 is one of the most commonly unearthed mutations, with more than 100 cases worldwide. “We need further research of CHAMP1 so we can understand how intellectual disability occurs, and to ultimately find a way to treat it,” said Tanaka.