Modeling the quantitative nature of neurodevelopmental disorders using Collaborative Cross mice

• DOI: 10.1186/s13229-018-0252-2
• Publication Date: 2018-12-13T13:31:34Z
• Authors: Remco T. Molenhuis; Hilgo Bruining; Myrna J. V. Brandt; Petra E. van Soldt; Hanifa J. Abu-Toa...; J. Peter H. Burbach; Fuad A. Iraqi; Richard F. Mott; Martien J. H. Kas
• Keywords: Genetic architecture; Human genetics; Animal model

Animal models for neurodevelopmental disorders (NDD) generally rely on a single genetic mutation fixed background. Recent human studies however indicate that clinical diagnosis with Autism Spectrum Disorder (ASD) is almost always associated multiple fore- and background changes. The translational value of animal model would be greatly enhanced if insults could studied in more quantitative framework across backgrounds. We used the Collaborative Cross (CC), novel mouse reference population, to investigate architecture behavioral phenotypes commonly NDD. Classical tests social recognition grooming appeared insufficient due dilution limited heritability. In contrast, digging, locomotor activity, stereotyped exploratory patterns were characterized by continuous distribution our CC sample also mapped trait loci containing genes corresponding populations. These findings show can move beyond comparative gene-single designs, point out which type are most suitable quantify effect developmental etiologies