Table 3. Molecular, Biochemical, Synaptic, and Behavioral Phenotypes of Shankl and Shank2 Mutant Mice.

	Shankl (Hung et al., 2008) (Silverman et al. 2011) (Wohr et al. 2011)	Shank2 (Won et al., 2012)	Shank2 (Schmeisser et al., 2012)
Exons/domain targeted	Exons 14-15/PDZ (Δex14-15)	Exons 6-7/PDZ (Δex6-7)	Exon 7/PDZ (Δex7)
Strain/Background	129SvJ ES cell and backcrossing to C57BL/6 for 3 generations	129SvJ ES cells and backcrossing to C57BL/6 for > 5 generations	129SV R1 ES cells and backcrossing to C57BL/6J for 10 generations
Age of mice tested	Biochemistry:3 months Morphology:E18 day for neuron culture and adult mice Electrophysiology:3-5 weeks Behavior:3-5 months	Biochemical:3-4 weeks Morphology:8-9 weeks Electrophysiology:3-9 weeks Behaviors:1-5 months	Biochemical:p25 and p70 days Morphology:E18 neuron culture and adult mice Electrophysiology:p21, p27, and 90 days Behaviors:6-8 months
Transcripts not disrupted	Predicted to be none	Predicted to be none	Predicted to be none
Genotype of mice analyzed	Homozygous, some heterozygous	Homozygous, some heterozygous	Homozygous, some heterozygous
Altered synaptic proteins	Reduced GKAP and Homer	Whole brain: Reduction of p- CaMKIIα/β (Thr286), p-ERK1/2, p-p38, p-GluA1 (Ser831 /S845), Increased GluN1	Hippocampus: increased GluN2B Striatum: increased GluN1, GluN2A, GluA2, SHANK3
Brain and synaptic morphology	CA1 hippocampus Reduced spine density, smaller and thinner PSD	CA1 Hippocampus Normal spine density No change in length and thickness of PSD	CA1 Hippocampus Reduced spine density, PSD structure normal
Synaptic physiology	CA1 Hippocampus Reduced AMPAR-mediated basal transmission. Normal mEPSC amplitude. Decreased mEPSC frequency, Normal paired-pulse ratio. Normal NMDA/AMPA ratio Normal LTP and LTD	CA1 Hippocampus No change in basal synaptic transmission and normal mEPSC Reduced NMDA/AMPAR ratio Reduced NMDAR dependent LTP and LTD. mGluR dependent LTD is normal Medial prefrontal cortex Normal NMDA/AMPA ratio	CA1 Hippocampus Reduced synaptic transmission Reduced mEPSC frequency. No difference for mEPSC amplitudes; Normal mIPSC frequency but slightly reduced mIPSC amplitudes, Normal sEPSC. The ratio of NMDA/AMPA is increased. Decreased I/O ratio. LTP is slightly enhanced but LTD is normal
Social behaviors	Reduced social sniffing by males in male-female interactions	Reduced interest in novel mice in non- social vs novel social pairing in 3 chamber test. Normal social recognition and normal olfaction.	Normal initiation for social contact but Impairment in maintaining social intact in resident-intruder test. Impaired social interaction in three chambers test. Normal olfaction
Ultrasonic vocalizations	Reduced calls by males in male- female reciprocal social interaction.	Male mice made less USV calls while females were presented and had longer latency for the first call	Female pup made more USV calls. No difference for USVs in adult during male-male interaction but reduced call and longer latency during female- female interaction
Repetitive behaviors	increased self-grooming and repetitive behaviors	Increased locomotor activity, No increased self-grooming in home cage but increased in novel objective recognition task. Females show repetitive jumping and reduced digging	Increased self-grooming/increased locomotor activity
Learning & memory	Enhanced spatial learning and memory task Impaired fear conditioning	Impaired spatial and learning and memory in Morris water maze. Novel objection recognition memory is normal.	normal working memory, novel objective recognition memory
Other behaviors	partial anxiety-like behavior; reduced scent marking behaviors	Increased anxiety-like behavior, impaired nesting behavior.	Increased anxiety-like behaviors,

AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; LTP, long-term potentiation; LTD, long-term depression; mEPSC, miniature excitatory postsynaptic current; mIPSC, miniature inhibitory postsynaptic current; NMDA, N-Methyl-D-aspartate; I/O, input/output; mGluR5, metabotropic glutamate receptor 5; N/A, not analyzed; USV, ultrasonic vocalization.