Genetic Modeling and Neurobehavioral Disorders: Focus on AutismComprehensive Guide to Autism

Preclinical research in neurobehavioral disorders strongly relies on the availability of robust animal models to the aim of understanding the pathophysiological alterations underlying these conditions and testing the potential efficacy of novel therapeutic approaches. Given that the etiopathogenesis of autism spectrum disorders has not been clearly elucidated so far and diagnosis is mainly based on presentation of three core behavioral symptoms (profound alterations in social interaction, communication deficits, and focused-stereotyped behaviors), different approaches have been adopted to model this neurodevelopmental disorder in rodents. The study of the behavioral phenotype has historically represented an invaluable tool for both the identification and the validation of potentially interesting models. In recent years, a major contribution in the generation of new models has been played by the continuous advances in the field of genetics and the development of gene-targeting procedures. This chapter provides an overview of the different approaches that have been adopted so far to model autism spectrum disorders and some related examples of currently available models of autism. In particular, a focus is made on genetic modeling of the disease, which is expected to be beneficial to the aim of uncovering unknown and potentially unpredicted genetic contributions to pathological phenotypes and to address the genetic hypothesis of autism. The need for developing new potential models and investigating further the existing ones, in order to fully recapitulate autism-related neuropathological signs and symptomatology, is also highlighted.