Assessing vision and autism spectrum disorder-relevant social interaction phenotypes in Dscam mice

Down syndrome cell adhesion molecule (DSCAM) is an immunoglobulin-superfamily cell-adhesion molecule important for neuronal survival, morphogenesis, synaptic specificity, and particularly retinal organization. Pathogenic variants in Dscam have been linked to developmental disorders including Autism Spectrum Disorder (ASD), Down Syndrome (DS), developmental delays and intellectual disabilities. Here we work to better understand the link between morphology and function in the nervous system by assessing the effects of Dscam mutations on both visual and ASD-relevant social interaction behaviors. While it is known that Dscam deficiency leads to perturbations in retinal organization, the subsequent effect on vision is not well studied. We found that homozygous conditional deletion of Dscam in the retina impacted optokinetic response and visual acuity; however, mice were still capable of image discrimination. In addition, Dscam heterozygous mice were used to test ASD-relevant social interaction and other phenotypes, matching the monoallelic human genetics of DSCAM variants in association studies. The Dscam heterozygous mice performed normally in the open field test, rotarod assay, forced swim test, and both the three chamber and dyadic social interaction assays. Overall, we found that our Dscam deficient mice provide a good model for exploring the relationship between retinal anatomy and visual behavior. However, heterozygous mice did not provide a good behavioral model for ASD. To fully understand the role of Dscam in neurodevelopment, additional functional and physiological studies will be necessary.