Strong evidence for genetic causes of autism has spurred the search for genes causing the disorder, and genetic mouse models offer an ideal experimental strategy to evaluate the consequences of candidate gene mutations. This study uses an inbred mouse strain (BTBR) with an autism-related phenotype to investigate the biological mechanisms underlying that phenotype. It will carry out a quantitative trait loci linkage analysis to discover genes that correlate with the autism-like phenotype. A second approach toward identifying the genes mediating the diagnostic symptoms of autism is to evaluate the behaviors of mice with experimentally targeted mutations in candidate genes for autism, including synaptic development genes neuroligin-2, neuroligin-4, shank1, and shank3, which have been associated with autism. The third component of this project is the translational evaluation of proposed treatments. The robust and highly replicated social deficits and repetitive self-grooming in BTBR mice provide a good model system for testing the ability of drugs and behavioral treatments to reverse and prevent autism-like symptoms. Both risperidone and MPEP, a metabotropic glutamate receptor antagonist, will be tested as well as a behavioral intervention. Development of mouse models with behavioral phenotypes relevant to core diagnostic symptoms of neuropsychiatric disorders such as autism may address the causes of mental illnesses and efficacies of novel treatments.