Rat Knockout Models of ASD
Baylor College of Medicine
The advent of transgenic technologies has revolutionized behavioral science. While mouse genetic models have been invaluable for studying underlying neurobiological mechanisms, mouse behavioral analyses have often been challenging. Until very recently, the use of rats as potential genetic models for disorders of the human CNS has not been realized because of the inability to readily manipulate their genome. Scientists at SAGE Labs have now developed a strategy for creating knockout (KO) rats and under a novel partnership with Autism Speaks are generating ones with mutation in ASD susceptibility genes. Currently rat models with mutations in Fmr1, Mecp2, Neurexin 1, Neuroligin 3, and MGluR5 have been created and additional lines are being generated. The investigators have developed a test battery for rats to study ASD-related behavioral responses. The battery includes assessments for ultrasonic communication, repetitive/perseverative responding, and social interactions. In addition, assays for anxiety-like responses and cognition, as well as a number of important control assays for activity and olfactory function are employed. The investigators have completed evaluations of Fmr1 and Neuroligin 3, and are in the process of completing studies with Mecp2, Neurexin 1 and mGluR5. This study evaluates three additional lines of rats on the standard test battery. The three lines include Shank3 and Shank2. Completed studies with Fmr1 and Neuroligin 3 have demonstrated a number of ASD-like traits including reduced play behavior and increased perseverative chewing. Research findings clearly indicate that rat KO lines will be an important research tool for future ASD research and the evaluation of potential therapeutic targets. Therefore, evaluating additional rat KO lines for ASD-like traits on a consistent behavioral-battery platform is necessary and important to continue to increase the number of genetically-modified rat models for scientists interested in ASD.