title: Modeling autism by SHANK gene mutations in mice.
abstract: Shank family proteins (Shank1, Shank2, and Shank3) are synaptic scaffolding proteins that organize an extensive protein complex at the postsynaptic density (PSD) of excitatory glutamatergic synapses. Recent human genetic studies indicate that SHANK family genes (SHANK1, SHANK2, and SHANK3) are causative genes for idiopathic autism spectrum disorders (ASD). Neurobiological studies of Shank mutations in mice support a general hypothesis of synaptic dysfunction in the pathophysiology of ASD. However, the molecular diversity of SHANK family gene products, as well as the heterogeneity in human and mouse phenotypes, pose challenges to modeling human SHANK mutations. Here, we review the molecular genetics of SHANK mutations in human ASD and discuss recent findings where such mutations have been modeled in mice. Conserved features of synaptic dysfunction and corresponding behaviors in Shank mouse mutants may help dissect the pathophysiology of ASD, but also highlight divergent phenotypes that arise from different mutations in the same gene.
authors.affiliation: Departments of Pediatrics and Neurobiology, Duke University School of Medicine, Durham, NC 27710, USA. yong-hui.jiang@duke.edu
authors.forename: Yong-Hui
authors.initials: YH
authors.lastname: Jiang
authors.forename: Michael D
authors.initials: MD
authors.lastname: Ehlers
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D057907:Post-Synaptic Density / Q000235:genetics / Q000473:pathology
chemical_list: D009419:Nerve Tissue Proteins; C122162:SHANK2 protein, human