Temporally Controlled Genetic Rescue of Shank3 Autism Model
University of Texas Southwestern Medical Center, Dallas
Basic & Clinical
Once a child with autism’s brain has fully developed, can the atypical brain function causing symptoms of autism be reverted back to typical brain function through medical treatment? If not, at what time during development of a child’s brain must we intervene to restore typical brain function to ameliorate the symptoms of autism? These are the fundamental questions that can be asked in a specific genetic animal model of autism. Some genetic forms of autism may be reversible by restoring normal function to the brain even after brain development has ended. Alternatively, intervention may be necessary prior to or during some critical period of brain development in order to make a lasting impact on brain function and autism symptoms. Multiple researchers have determined that mutations in the SHANK3 gene cause some cases of autism. The research team has developed and characterized an animal model of SHANK3 autism-related mutation that has some social deficits and specific changes in how connections in the brain (synapses) function. More recently, they developed an animal model with the autism-causing Shank3 mutation that can revert back to the typical form of SHANK3 at any point in time just by giving the animal a designer drug for a short time. This animal model permits study of whether reversing an atypical, autism-causing gene mutation back to a typical, non-mutated gene can restore typical synaptic function and typical behavior to the model. This Pilot study aims to establish the feasibility of reversing Shank3 mutant mice back to normal Shank3 after brain development is complete and identify which synaptic function differences and which behavioral differences are rescued. This approach has worked previously in the MeCP2 mutant model of Rett Syndrome, an Autism Spectrum Disorder related to autism. Understanding when during development a genetic or drug treatment must be given is a critical decision point for treating autism. This research, limited in this Pilot to Shank3 linked forms of autism and not broader, related disorders, has the potential to yield a technically advanced way to address this decision point in the most direct manner possible.