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.
The R1117X Shank3 knock-in allele harbors the schizophrenia-associated R1117X mutation in Shank3 exon 21 that creates a stop codon and results in expression of a ~122 kDa truncated SHANK3 protein.
R1117X Shank3 mice on a mixed C57BL/6J;129S genetic background were characterized in the original publication (Zhou et al. 2016 Neuron 89:147); and this is described below.
The donating investigator reports that mice homozygous for the R1117X Shank3 knock-in allele (R1117X+/+) are viable and fertile, but are inefficient breeders. Homozygotes exhibit synaptic and behavioral phenotypes similar to human schizophrenia. Specifically, R1117X+/+ exhibit profound synaptic defects in prefrontal cortex, social dominance behavior and increased level of anxiety-like behavior. Heterozygous mice (R1117X+/-) have ~50% of the wildtype levels of full-length SHANK3 protein, and exhibit a less severe phenotype.
