In this strain, a neo cassette replaces exons 4-9 of SH3/ankyrin domain 3 (Shank3) gene. SHANK3 is a synaptic scaffolding protein, expressed in the postsynaptic density (PSD) of excitatory synapses, which contains five intragenic promoters allowing for extensive alternative splicing. SHANK3 mutations have been identified in cases of intellectual disability such as autism spectrum disorder (ASD), Phelan-McDermid syndrome, and Schizophrenia. In these Shank3e4-9 mice, the neo cassette is inserted downstream of Promoter 2, making these mice deficient in Shank3a-b which are transcripts from Promoters 1-2. They do produce transcripts Shank3c-e from downstream Promoters 3-5. These mice display abnormal social behaviors, communication patterns, repetitive behaviors, learning and memory. Male mice also display severe motor coordination impairments. Shank3e4-9 mice also exhibit morphological alterations in dendritic spines and are deficient in long-term potentiation. Homozygotes are viable and fertile.These mice may be useful for studying behavioral abnormalities associated with ASD.

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Shank3e4-9 has a neo cassette replacing the ankyrin repeat domains (exons 4-9) of the Shank3 gene. Homozygous mice display abnormal social behaviors, communication patterns, repetitive behaviors, learning and memory. These mice may be useful for studying behavioral abnormalities associated with autism spectrum disorder.

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