Mouse Models as Translational Tools to Discover Treatments for Autism Spectrum Disorders: Focus On Rapamycin

The use of mice as genetic tools to study the molecular basis of brain development and function has grown steadily over recent years. Recent human genetic studies have implicated the PI3 Kinase pathway as an underlying cause of a small subset of autism cases that are related to genetically inherited diseases.  Using mutant mouse models, we have shown that modulation of the PI3 Kinase pathway can be an indirect source of synaptic modulation. Moreover, mice lacking PI3 Kinase components in mature neurons exhibit stereotypic behavioral abnormalities reminiscent of autism.  Because this signaling pathway is also implicated in many human cancers, drugs that inhibit this pathway are in development.  We have applied such drugs, including the specific mTORC1 inhibitor rapamycin in Pten mutant mice, with promising outcomes. It is our hope that continued study of these mice will provide insights into the anatomical and cellular basis of at least a subset of autism spectrum disorders.