Document Type
Journal Article
Publication Date
2018
Journal
Frontiers in Genetics
Volume
9
Inclusive Pages
65
DOI
10.3389/fgene.2018.00065
Abstract
Hundreds of genes are mutated in non-syndromic intellectual disability (ID) and autism spectrum disorder (ASD), with each gene often involved in only a handful of cases. Such heterogeneity can be daunting, but rare recessive loss of function (LOF) mutations can be a good starting point to provide insight into the mechanisms of neurodevelopmental disease. Biallelic LOF mutations in the signaling scaffold CC2D1Acause a rare form of autosomal recessive ID, sometimes associated with ASD and seizures. In parallel, we recently reported that Cc2d1a-deficient mice present with cognitive and social deficits, hyperactivity and anxiety. In Drosophila, loss of the only ortholog of Cc2d1a, lgd, is embryonically lethal, while in vertebrates, Cc2d1a has a homolog Cc2d1b which appears to be compensating, indicating that Cc2d1a and Cc2d1b have a redundant function in humans and mice. Here, we generate an allelic series of Cc2d1a and Cc2d1b LOF to determine the relative role of these genes during behavioral development. We generated Cc2d1b knockout (KO), Cc2d1a/1b double heterozygous and double KO mice, then performed behavioral studies to analyze learning and memory, social interactions, anxiety, and hyperactivity. We found that Cc2d1a and Cc2d1b have partially overlapping roles. Overall, loss of Cc2d1b is less severe than loss of Cc2d1a, only leading to cognitive deficits, while Cc2d1a/1b double heterozygous animals are similar to Cc2d1a-deficient mice. These results will help us better understand the deficits in individuals with CC2D1A mutations, suggesting that recessive CC2D1B mutations and trans-heterozygous CC2D1A and CC2D1B mutations could also contribute to the genetics of ID.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
APA Citation
Zamarbide, M., Oaks, A., Pond, H., Adelman, J., & Manzini, M. C. (2018). Loss of the Intellectual Disability and Autism Gene Cc2d1a and Its Homolog Cc2d1b Differentially Affect Spatial Memory, Anxiety, and Hyperactivity. Frontiers in Genetics, 9 (). http://dx.doi.org/10.3389/fgene.2018.00065
Peer Reviewed
1
Open Access
1
Included in
Genetics and Genomics Commons, Medical Pharmacology Commons, Medical Physiology Commons, Pharmacology Commons, Physiology Commons
Comments
Reproduced with permission of Frontiers Media S.A. Frontiers in Genetics