Shank3 transgenic mice overexpress a wild-type mouse Shank3 (SH3/ankyrin domain gene 3) gene and EGFP directed by Shank3 promoter/enhancer regions on the BAC transgene. SHANK3 is a synaptic scaffolding protein, expressed in the postsynaptic density (PSD) of excitatory synapses. SHANK3 mutations have been identified in cases of intellectual disability such as autism spectrum disorder (ASD), Phelan-McDermid syndrome, and Schizophrenia. These Shank3 transgenic mice express 1.2-fold to twofold higher levels of each of the three major Shank3 isoforms (α, β and γ), with 50% more total Shank3 protein in dendritic spines in the cortex, hippocampus and striatum. Hemizygous mice are viable and fertile. They display a hyperkinetic phenotype that resembles mania. They exibit increased locomotor activity and speed in the open field test, and hyperactivity which was aggravated after injection of amphetamine. Shank3 transgenic mice also display a lower duration of immobility during the tail-suspension test, elevated acoustic startle response with reduced prepulse inhibition (PPI), abnormal circadian rhythms, decreased social interactions, seizures, and hyperphagia-like behavior. Transgenic mice responded well to the anticonvulsant drug valproate.
