The 16p11.2 deletion and duplication syndromes are frequent copy number variants (CNVs) in humans associated with developmental delay and autism spectrum disorder (ASD). 16p11.2 deletion and duplication syndromes correspond to the loss or gain, respectively, of one copy of the genetic interval located between two low-copy repeats. Genes within the 16p11.2 region have been found to be highly conserved on mouse chromosome 7, and mouse models carrying deletion or duplication of the region homologous to the human 16p11.2 region have been generated by Yann Herault’s laboratory¹ and others^2,3. These mouse models all share similar phenotypic deficits in novel environment exploration, object recognition and context discrimination. By exploring the impact of the genetic context, Herault’s lab also found social interaction deficits in both deletion and duplication mice in a mixed genetic background.

Genes within the human 16p11.2 region are also highly conserved on rat chromosome 1, and the rat is a more sociable species than the mouse and has a larger spectrum of available behavioral assessments. Therefore, in order to generate an animal model with potentially more relevance to the human condition, Herault’s laboratory recently used CRISPR/Cas9 technology to engineer Sprague-Dawley outbred line rats with a deletion or duplication of the homologous region to the human 16p11.2 genetic interval.

Herault’s team aims to test if these rat 16p11.2 deletion and duplication models recapitulate the mouse phenotypes. They will also investigate additional communication and sociability phenotypes in these rat models. Once validated, these new 16p11.2 animal models will provide researchers with additional experimental systems in which to assess candidate drug therapies for 16p11.2 CNV syndromes.

1. Arbogast T. et al. PLOS Genet. 12, e1005709 (2016) PubMed
2. Portmann T. et al. Cell Rep. 7, 1077-1092 (2014) PubMed
3. Horev G. et al. Proc. Natl. Acad. Sci. USA 108, 17076-17081 (2011) PubMed