This project aims to develop a new rat model corresponding to the deletion of the 16p11.2 BP4-BP5 homologous region in the Long-Evans (LE) strain. Yann Herault previously developed and characterized, with support from a prior SFARI award, a 16p11.2 deletion rat model in the outbred Sprague Dawley (SD) strain.

The expertise gained from that earlier project will now be applied to the development and characterization of a new model in the LE background, since this is often the strain of choice for cognitive, behavioral and systems neuroscience studies. Needless to say, both the LE and SD models will be on an outbred genetic background. Thus, they both have inherently more variability that more closely mimics conditions observed in the human population compared to mouse models of 16p11.2 deletion, which have largely been engineered on inbred backgrounds. Hence, both rat models should prove useful for characterizing cellular and behavioral phenotypes relevant for 16p11.2 deletion syndrome.

The new LE rat model will be instrumental for many different studies, including behavioral analyses (e.g., learning and memory experiments to study intellectual disabilities and social interaction paradigms to study phenotypes relevant to autism) and the validation of therapies. Furthermore, Herault and his colleagues anticipate that the comprehensive molecular and comparative analyses of the rat and mouse models that will be performed in the Mouse Clinical Institute (Institut Clinique de la Souris), in addition to comparisons to the clinical diagnoses of individuals with the condition, has the potential to foster the development of novel therapeutic approaches.