Animal Models of Autism: Pathogenesis and Treatment
University of Texas Southwestern Medical Center, Dallas
Basic & Clinical
Mutations in the neuroligin gene have been implicated in a subset of autism cases. Neuroligin is a cell-adhesion molecule found at synapses, which are connection points between neurons. Neuroligin molecules form a bridge across these synaptic connections by binding to a molecule called neurexin. Thus, mutations in neuroligin could disrupt neural connectivity. This research project will introduce the autism-related neuroligin mutation in mice. These mice will have the very same genetic cause of autism as a subset of autism patients. Experiments will test these mice for behavioral and neural abnormalities that may be related to autism. Preliminary data suggest that these mice exhibit specific deficits in social interaction, yet also exceed normal mice on one measure of learning and memory function. In addition to behavioral analyses, the project will also assess neural function in these mice, particularly at the level of the synapse. What this means for people with autism: These studies will create a novel animal model of autism based on known human genetic causes of the disorder. Discovering how this genetic abnormality leads to changes in the biology (that result in the behavioral symptoms in this model) can identify potential new targets for disease treatment.