Creating an advanced transgenic animal model of autism

Autism is a highly genetic developmental brain disorder which is characterized by social impairments. Autism affects 1 in 68 US children, with an annual cost in the US of $236 billion dollars. Unfortunately, the basic biology of autism remains poorly understood. Consequently, there are currently no laboratory tests to detect, nor effective medications to treat, autism’s disabling social deficits. Barriers to progress include the inability to directly study brain tissue in patients, and the fact that mice are poor models because they lack the complex social capabilities found in humans. There is thus tremendous value in creating transgenic marmosets, with stable large deletions (copy number variants; CNVs) in their genomes that resemble large CNVs found in humans, and which strongly predispose for autism. During this two year project we will produce the required basic proof-of-principle data by stably and precisely engineering relevant large deletion CNVs into the genome of marmoset stem cells. Future development of this model, including creation of a transgenic marmoset colony at Stanford, will seek to accelerate the discovery of autism biomarkers and novel drug targets, and streamline the development of the first effective medications to improve social functioning in people with autism.