Table 5.
Synaptopathy ASD models.
| Mouse | Molecular function | Phenotype | Suggested mechanism | Potential therapeutics | References | |||
|---|---|---|---|---|---|---|---|---|
| Social interaction | Social communication | Repetitive behavior | Other phenotypes | |||||
| NLGN1 KO | Synaptic adhesion molecule | Minimal impairment | NA | Grooming | Learning deficits | NMDAR hypofunction | D-cycloserine | Blundell et al., 2010 |
| NLGN2 Tg | Impaired | NA | Jumping | Seizure (EEG) | Increased GABAergic transmission | NA | Hines et al., 2008 | |
| NLGN3 R451C KI | Impaired | Increased calls | NA | Enhanced learning | Increased GABAergic transmission | NA | Tabuchi et al., 2007 | |
| NLGN3 KO | Impaired | Reduced calls | Normal behavioral flexibility | Hyperactivity | Decreased brain volume, Cerebellar deficit | NA | Radyushkin et al., 2009; Baudouin et al., 2012; | |
| NLGN4 KO | Impaired, Less aggression | Reduced calls | Normal | NA | Decreased brain volume | NA | Jamain et al., 2008 | |
| Shank1 KO | Synaptic scaffolding protein | Not impaired | Not impaired | Not impaired | Anxiety, Motor deficits | Impaired glutamatergic transmission | NA | Hung et al., 2008; Silverman et al., 2011 |
| Shank2exon7 KO | Impaired | Reduced calls, Pattern change | Grooming | Hyperactivity, Anxiety | NMDAR hyperfunction | NA | Schmeisser et al., 2012 | |
| Shank2exon6-7 KO | Impaired | Reduced calls | Jumping | Hyperactivity, Anxiety | NMDAR hypofunction | CDPPB, DCS | Won et al., 2012 | |
| Shank3 HT | Impaired | Reduced calls | NA | NA | Impaired glutamatergic transmission | Ampakine, IGF-1 | Bozdagi et al., 2010 | |
| Shank3B KO | Impaired | NA | Grooming | Anxiety | Striatal dysfunction | NA | Peca et al., 2011 | |
| Shank3exon4-9 KO | Impaired | Pattern change | Grooming | Learning deficits | Impaired glutamatergic transmission | NA | Wang et al., 2011 | |
| Cadps2 KO | Ca2+-dependent secretion activating protein | Impaired, Maternal neglect | NA | NA | Hyperactivity, Anxiety | Decreased density of PV interneuron, Reduced BDNF release | BDNF | Sadakata et al., 2007 |
| Syngap1 HT | GTPase-activating protein for Ras small GTPase | Normal social interaction, Impaired social recognition, Propensity toward social isolation | NA | Stereotypy (repeated single beam break within 1 s) | Learning deficits, Hyperactivity, Anxiolytics, Abnormal sensory-motor gating | Premature spine maturation and hyperexcitability | NA | Guo et al., 2009; Clement et al., 2012 |