Table 1.

Mouse models of ASD.

Category	Gene Symbol	Molecular Function/Copy Number	Molecular, Cellular and Circuit Phenotypes	Refs
Genetic animal models	NRXNs	Synaptic adhesion molecule	↓Glutamatergic trans. and synaptic density	[7,8,9,10]
	NLGNs	Synaptic adhesion molecule	Context-dependent impaired glutamatergic and GABAergic trans; ↓Brain volume, cerebellar deficit; ↓GABAergic trans. in D1-MSN in NAc; ↓Brain volume	[11,12,13,14]
	SHANK3	Synaptic scaffolding molecule	Striatal dysfunction; ↓Activity-dependent AMPAR distribution and LTP; ↓Glutamatergic trans. by presynaptic mechanism, ↓LTP; ↓NMDAR function, Rac1, PAK, cofilin signaling defects, F-actin dysregulation in PFC	[15,16,17,18,19]
	TSC1/2	Translational regulator	Cerebellar deficits; Brain enlargement, hyperactive mTOR signaling, autophagy deficiency	[20,21,22]
	FMR1	Translational regulator	↑mGluR function, immature protrusion; PI3K signaling, ↑spine density, impaired AMPAR-mediated synaptic plasticity; Hypersensitivity to ERK1/2 pathway activation, ↑protein synthesis; ↑Fetal or early postnatal GABA and Cl–, abnormal EEG	[23,24,25]
	MECP2	Translational regulator	↓Dopamine transporter (DAT) and tyrosine hydroxylase (TH) in the striatum; Altered cortical and cerebellar volumes; Cortical LTP deficit; ↓cortical BDNF levels; Impaired PI3K/AKT/mTOR pathway; ↓CB1 and CB2 receptor levels; Hippocampal circuit dysfunction	[26,27,28,29]
	CHD8	Translational regulator	CHD8 regulates different sets of genes associated with ASD by direct and indirect mechanisms	[30,31,32]
	SCN1A	Na+ channel	↓GABAergic interneuron firing	[33]
	SYNGAP1	Alternative splicing	Major constituent of the PSD essential for postsynaptic signaling; SYNGAP1 regulates the postmitotic maturation of human neurons made from hiPSCs, which influences how activity develops within nascent neural networks	[34,35]
	ADNP	Translational regulator	Potential transcription factor; mediate some of the neuroprotective peptide VIP-associated effects involving normal growth	[36]
	ANK2	Protein transport	endocytosis and intracellular protein transport; continuous directional cell migration	[37]
	CUL3	Transport	Mediate ubiquitination of target proteins; releases the GATOR1 complex-mediated inhibition of the TORC1 pathway	[38]
	PTEN	Apoptosis	Neuron positioning, dendritic development and synapse formation	[39]
	TBR1	Transcription	Neuronal migration, laminar and areal identity, and axonal projection; blocks the formation of the corticospinal (CS) tract from layer 6 projection neurons	[40]
	SCN2A	Ion transport	Mediates the voltage-dependent sodium ion permeability of excitable membranes	[41]
	TRIP12	DNA repair	Ubiquitin fusion degradation (UFD) pathway and	[42]
			regulation of DNA repair
	RELN	Cell adhesion	Regulates microtubule function in neurons and neuronal migration; affects migration of sympathetic preganglionic neurons in the spinal cord	[43]
	UBE3A	Proteolysis	Acts as a regulator of synaptic development by mediating ubiquitination and degradation of ARC; Synergizes with WBP2 in enhancing PGR activity	[37]
	Cntnap2	Cell adhesion	Plays a role in the formation of functionally distinct domains critical for saltatory conduction of nerve impulses in myelinated nerve fibers	[44]
	Grin2b	Ion transport	Irreversible neuronal death; neural pattern formation; long-term depression (LTD) of hippocampus membrane currents and in synaptic plasticity	[45,46]
Copy number variation	15q11-q13	Deletion	↑excitatory synaptic event frequency amplitude, density of dendritic protrusions,↓inhibitory synaptic transmission; Impaired activity-dependent synaptic plasticity and homoeostatic synaptic scaling	[47,48]
	15q13.3	Microdeletion	↑endoplasmic reticulum stress; Dysregulated neuronal gene expression; ↑cholinergic activity; ↑homomeric CHRNA7 channel activity	[49,50]
	16p11.2	Deletion	↑soma size and dendrite length in 16pdel neurons; ↓neuronal size and dendrite length in 16pdup neurons; ↓synaptic density	[51,52]
	22q11.2	Duplication	↓spontaneous neuronal activity and calcium signalling; ↓expression of miR-1290	[53]
Idiopathic animal models	BTBR-T+ tfl/J		↓GABAergic inhibitory transmission; ↓5HT2A receptor density and activity; ↑glutamatergic transmission in cortico-striatal circuitry; Impaired dopamine D2 receptor function; ↓BDNF expression in hippocampus and cortex; Absence of corpus callosum, lack of hippocampal commissure; ↓cortical thickness; ↓cerebral white and gray matter; Impaired cortico-thalamic function; Altered volumes of cerebellum, brainstem, striatum, and hippocampus	[54,55,56,57,58,59]
	BALB/cByJ		Interleukin change; neuroinflammation	[60]
Environmental models	VPA		↑glutamatergic excitatory signaling; Hyperexcitable local connectivity;↓parvalbumin-positive inhibitory interneurons;↑brain serotonin levels; Apical dendritic arborization complexity;↓PTEN expression and↑p-AKT protein levels in hippocampus and cortex	[61,62,63,64]
	Maternal immune activation		Changes of various interleukins in brain	[65]