Mice containing a human chromosome 15 (Tc15 mice) model behavioral impairment.. Mus musculus

ASD is a complex group of neurodevelopmental disorders characterized by impairments of reciprocal social interactions, problems in communication, and a restricted range of behaviors and interests. Current microarray-based technologies that enable detection of submicroscopic microdeletions and microduplications (CNVs) have revealed that submicroscopic CNVs can have a pathogenic role in ASD. After fragile X, maternal 15q11-q13 duplications are the most common cytogenetic cause of autism, occurring in approximately 1-3 percent of individuals with ASD. In this project, we focused on the 15q11-q13 locus to define the molecular basis of the CNVs effects on neurodevelopment. Microcell-mediated chromosome transfer (MMCT) was used to create embryonic stem (ES) cells containing a human chromosome15 (Chr.15). ES cell lines retaining a Chr.15 were used to produce the transchromosomic mice (Tc15 mice) with a single human chromosome15. The Tc15 mice grew normally and were fertile with no overt phenotypes. In this project, we examined several behavioral experiments in Tc15 mice to test whether the paternal duplications cause autistic-like phenotypes. Our behavioral experiments demonstrated several abnormal behavioral phenotypes, not autism-like phenotype in Tc15 mice. Thus, Tc15 mice accurately might recapitulate non-autistic phenotypes that are observed in paternal human 15q duplication patients. For further analysis we need to know whether the maternal duplications cause autistic-like phenotypes in Tc15 mice.