TABLE 1.

Patients’ phenotypes, as well as phenotypes and rescue strategies shown in ASD mouse models.

	Genes	Human phenotype	Mouse phenotype	Cellular phenotype	Rescue strategy	Rescued phenotype	References
Synaptic network	SHANK3	Speech-defective ASD, Phelan-McDermid syndrome, Schizophrenia	Core ASD symptoms, Anxiety	Hyperactive mGluR5 activity	MPEP (mGluR5 antagonist)	Grooming, Instrumental learning, Striatal synaptic plasticity	Wang et al., 2016
					LSD1 (H3K4me2 demethylase inhibitor)	Core symptoms	Rapanelli et al., 2022
					Rapamycin, CLK2 inhibitor, Akt activator, IGF-1	Social behavior	Bidinosti et al., 2016
					Adulthood correction with SHANK3 expression	Core symptoms	Mei et al., 2016
					IL-17a	Social behavior	Reed et al., 2020
	CNTNAP2 (NRXN4)	Speech-defective ASD, AR Pitt-Hopkins-like syndrom I	Core ASD symptoms	Projection neuron mismigration, Reduced GABAergic neurons and oxytocin neurons	Oxytocin	Social behavior	Penagarikano et al., 2015
					Ro27-3225 (melanocortin receptor 4 agonist)	Social behavior	Penagarikano et al., 2015
					CX546 (positive allosteric modulator of AMPA receptor)	Social interaction	Sacai et al., 2020
					IL-17a	Social behavior	Reed et al., 2020
					Risperidone	Repetitive behavior	Penagarikano et al., 2011
	NLGN3	GOF – X-linked ASD or Asperger syndrome	GOF – Impaired social interaction, KO – Fragile X syndrome	KO – Impaired corticostriatal gltamatergic synapses, E:I imbalance	Adulthood conditional correction with WT NLGN3 in the Purkinje cells	Synaptic plasticity	Baudouin et al., 2012
					Cannabinoid	Synaptic plasticity	Martella et al., 2018
Neuronal signaling	PTEN	ASD, Oncological syndromes	Impaired social interaction	Upregulation of the Akt-mTOR pathways, Downregulation of GSK3	Rapamycin (supression of mTORC1)	Social behavior	Zhou et al., 2009
					Reduced Rictor expression (suprression of mTORC2)	Social behavior	Zhou et al., 2009
	TSC1/TSC2	ASD, Tuberous sclerosis-1	Core ASD symptoms, Seizures	Increased number of astrocytes, Early increase of GABAergic interneurons	Rapamycin (supression of mTORC1)	Seizure, Social behavior	Zeng et al., 2008
	UBE3A	Maternal LOF – Angelman syndrome, Paternal duplication – ASD	Double or triple dose – Core ASD symptoms	Increased dose of UBE3A – Downregulation of glutamatergic synapse	Cbln1 genetic expression	Social interaction	Krishnan et al., 2017
Transcriptional and Chromatin Remodeling	CHD8	ASD (macrocephaly, distinct facial features, gastrointestinal motility)	Core ASD symptoms, Abnormal brain structure, Anxiety	Downregulation of Wnt signaling	Genetic restoration of β-catenin	Social behavior	Chahrour et al., 2008
	MECP2	ASD, Rett syndrome	Impaired social behavior, Anxiety, Learning and memory deficit	Impaired GABAergic neurons, Decrease of BDNF expression	GABAA receptor agonist	Social behavior, Anxiety, but not Memory	Chang et al., 2006
					IGF-1	Motor function, Breathing pattern	Tanaka et al., 2012
					BDNF	Motor function, Electrophysiological deficits	Hogart et al., 2007