Rett Syndrome is an autism-related disorder that affects primarily girls and has a prevalence of 1 in 10,000 births. Restoring function of the gene responsible for Rett Syndrome, Mecp2, to mutant mice allows them to live normal, healthy lives, even after symptoms have developed. This is hopeful news for patients, highlighting a potential for reversing the disease by pharmacologic means. Unfortunately, Mecp2 is not a promising drug target, as a genetic trick that would be impossible in humans is required to restore function in mice. Our lab has undertaken a genetic screen in which we randomly mutated a second genomic site in Mecp2-mutant mice to locate more pharmacologically targetable genes. From this screen, we have identified five lines carrying inherited suppressors that increase lifespan and decrease other Rett Syndrome related symptoms in Mecp2-mutant mice. This project focuses on characterizing the two mutations present in the line that show the greatest degree of rescue - one of which, we believe, provides great therapeutic promise. In the process of assessing the degree of rescue for each line, we will evaluate the brain structures altered in Rett Syndrome to determine the degree to which neuronal maturation deficits are rescued. Furthermore, we will use established mouse behavior tests to assess the extent to which the suppressors alter cognitive ability and motor function. Understanding the suppressors at a functional molecular level may provide an avenue for development of therapeutic compounds applicable to multiple types of autism spectrum disorders.
Interagency Autism Coordinating Committee (IACC)
Autism Research Database (AFD)
