The deletion of 27 genes in the 16p11.2 chromosomal region is associated with autism spectrum disorders, intellectual disability and obesity. To study the underlying cellular, molecular and anatomical basis of autism, Ricardo Dolmetsch and his colleagues at Stanford University in California have generated a mouse that lacks the same 27 genes on a corresponding chromosome in the mouse genome. Their goal, in collaboration with Jacqueline Crawley’s lab, is to characterize the neuroanatomical, neurophysiological and behavioral features of these mice.

The researchers at Stanford are conducting a series of studies that include characterization of gross brain anatomy and volume using a combination of magnetic resonance imaging and postmortem brain slices. They are also investigating the regional distribution of neuronal cell types using immunohistochemistry, and a new technology that uses massively multiplexed single-cell PCR to identify cell populations in specific regions of the brain. They are using slice electrophysiology to measure the basic electrophysiological features of neurons in the cortex and striatum regions of the mouse brain.

Crawley and her coworkers at the University of California, Davis MIND Institute are planning to conduct comprehensive behavioral assessments of these mice to measure social interactions, communication, repetitive behaviors, developmental milestones, learning and memory, hyperactivity, anxiety-like traits, sensory sensitivity and motor abilities. Their studies may uncover relevance to the varied symptoms of the human 16p11.2 deletion syndrome.

Through these integrated studies, Dolmetsch and Crawley aim to identify the neuroanatomical, functional and behavioral consequences of heterozygous loss of the 27 genes in the 16p11.2 deletion region. This information could set the stage for developing diagnostic tools and for testing novel therapeutics for autism spectrum disorders.