Viral expression of a dominant-negative form of Rac1 following bilateral injection into the prelimbic regions of wild-type mice resulted in ASD-like social deficits and reduced NMDAR-ESPC in PFC pyramidal neurons; conversely, viral expression of constitutively active Rac1 in SHANK3-deficient mice rescued ASD-like social deficits and NMDAR hypofunction (Duffney et al., 2015). De novo ASD-associated missense variants in the TRIO gene were experimentally shown to affect Rac1 activiation in two studies (Sadybekov et al., 2017; Katrancha et al., 2017). De novo missense variants in the RAC1 gene were identified in seven individuals presenting with intellectual disability and brain malformations; two of these individuals presented with stereotypic movements, and one was diagnosed with autism (Reijnders et al., 2017). Ma et al., 2022 recently demonstrated that bidirectional dysregulation of Rac1 activity in the medial prefrontal cortex (mPFC) dictated shared social deficits in mice.
Molecular Function
The protein encoded by this gene is a GTPase which belongs to the RAS superfamily of small GTP-binding proteins. Members of this superfamily appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Autism-like Deficits in Shank3-Deficient Mice Are Rescued by Targeting Actin Regulators.
