| 58234 | Q4ACU6 | SHAN3_MOUSE | SH3 and multiple ankyrin repeat domains protein 3 (Shank3) (Proline-rich synapse-associated protein 2) (ProSAP2) (SPANK-2) | DISRUPTION PHENOTYPE | Animals deficient for isoforms 1-7 exhibit self-injourious repetitive grooming and deficits in social interaction. They show defects at striatal synapses and cortico-striatal circuits with an increase in striatal volume, dendritic length, and surface area and a decrease of spine density, length and thickness of PSD. They seem to have an altered molecular composition of postsynaptic machinery in the striatum (PubMed:21423165). In contrast, animals deficient for isoforms 1 and 2 exhibit a normal initiation of social interaction with a perturbed recognition of social novelty (PubMed:21423165). In PubMed:21558424, animals deficient for isoforms 1 and 2 show abnormal social behaviors, communication patterns, repetitive behaviors, learning and memory. In CA1 hippocampus, the synaptic plasticity is impaired with longer dendritic spines, decreased spine density and deficient long-term potentiation. The expression of specific synaptic scaffolding proteins and receptor subunits are altered. Animals deficient for isoforms 1-5 exhibit self-injourious repetitive grooming, brain-region-specific up-regulation of ionotropic glutamate receptors and increased levels of SHANK2 (PubMed:22699619). Animals deficient for predominant isoforms containing exon 21 exhibit motor-coordination deficits, hypersensitivity to heat, novelty avoidance, altered locomotor response to novelty and minimal social abnormalities. They show a decrease in NMDA-AMPA excitatory postsynaptic current ratio in hippocampal CA1, reduced long-term potentiation and deficits in hippocampus-dependent spatial learning and memory (PubMed:24259569). {ECO:0000269|PubMed:21423165, ECO:0000269|PubMed:21558424, ECO:0000269|PubMed:22699619, ECO:0000269|PubMed:24259569}. |