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Page 6 of 13 Zhang et al. Ageing Neur Dis 2023;3:24 https://dx.doi.org/10.20517/and.2023.18

Mouse/C57BL/6 KO - Exon 21 - Neuronal morphology appeared unaltered - Impaired spatial learning, poor motor coordination, [40]
(PRO)/homozygous - No differences in spine density and shape avoidance towards inanimate objects, and excessive
- Loss SHANK3 protein - Impaired long-term potentiation self-grooming in advanced adulthood
(> 150 Kd) - No alterations in ultrasonic vocalizations
Mouse/C57BL/6N KO - Exon 9 - Reduced excitatory transmission and increased mIPSC - Not autistic-like behavior [41]
(ANK)/heterozygous frequency in hippocampus - Increased rearing in a novel environment
- Loss of shank3a - Decreased mIPSC frequency but normal mEPSCs in mPFC - Mildly impaired spatial memory
Mouse/C57BL/6J KO - Exon 21 - No change in glutamate receptor or Homer1b/c expression in - Impaired motor learning and coordination [43]
G/G
(PRO)/homozygous whole shank3 mice hippocampal lysates - An avoidance phenotype towards inanimate objects
- Loss of SHANK3 isoforms - Decreased phosphorylation of the GluN2B Tyr1472 site - Aberrant locomotor activity in response to novelty
(> 150 Kd) - Not express an anxiety-like phenotype
- Minimal spatial learning differences
- Not display social interaction deficits
- Normal grooming
Mouse/C57BL6/S129sv KO - Exon 21 - No change of mEPSC frequency and AMPA to NMDA current - Social interaction deficit, but it did not reach statistical [42]
(PRO)/homozygous ratio significance
- Expressed SHANK3 - Reduced Homer protein, PSD93, SynGAP
(122 kDa) - Reduced NMDA receptor subunits
- R1117X mutation - Not see a trend of upregulation of any of the synaptic proteins
tested
- Reduction of mEPSC amplitude
- Reduction of the spine density layer 2/3 pyramidal neurons in
the frontal association area
Mouse/C57BL6/S129s KO - Exon 21 - No change of mEPSC and AMPA to NMDA current ratio - An early-onset social interaction deficit
(PRO)/homozygous frequency [42]
- An almost complete loss of - Increase of mEPSC amplitude
SHANK3 protein - Reduced Homer protein, GluR1, SynGAP, SHANK2, and
- InsG3680 mutation NMDA receptor subunits
- No significant differences in either frequency or amplitude of
mEPSC
- Reduction of the spine density of layer 2/3 pyramidal neurons
in the frontal association area
Mouse/C57BL/6J KO - Exons4-22 (ANK, PDZ, - NAC firing deficit - Core behavioral features of ASDs [44]
PRO)/homozygous - Abnormalities in brain structure - Intact fear learning
- Loss of all known SHANK3 - Dysfunctional striatal synapses - Mildly perturbed hippocampal spatial memory
protein isoforms - Severely impaired striatal learning
- Abnormal ultrasonic vocalizations
Rat/Sprague Dawley KO - Exon 6 - Induced LTP - Impairs long-term social memory [45]
(ANK)/heterozygous - Normal social interaction
- Loss of shank3a - Attention deficits
Rat/Sprague Dawley KO - Exon 6 - Induced LTP - Impairs long-term social memory [46]
(ANK)/heterozygous - Normal social interaction
- Loss of shank3a -Attention deficits
Rat/Charles River Laboratories KO - Exons11-21 (PDZ, SH3, - Reduced spine density, PSD-95 - Normal social interaction behavior
PRO)/homozygous - Reduced Homer and NR1 in homogenates from the striatum - Impaired social memory and learning memory
- Loss of all known SHANK3 - Increased PSD-95 in the hippocampal PSD fraction of - Increased anxiety behavior and pain threshold
protein isoforms heterozygous rats - Self-grooming behavior and skin lesions
- NR1 increased in the hippocampal homogenate fraction of
heterozygous rats