Table 1 Repetitive behaviors and neuronal phenotypes in ASD mouse models
Type of repetitive behaviors | Model mouse | Biological functions of the target protein | Other behavioral characteristics | Implicated brain regions and neural phenotypes | Rescue of repetitive behaviors |
|---|---|---|---|---|---|
Self-grooming | BTBR TÂ +Â tf/J (inbred strain) [16] | Â | Hyperactive | Decreased sIPSC and increased sEPSC frequency in the hippocampus [27] No corpus callosum [24] | Repetitive self-grooming and E/I balance with GABA-R agonists such as clonazepam [34] Repetitive self-grooming with mGluR5 antagonism [32, 33] Repetitive self-grooming with a NMDA-R agonist, d-cycloserine [85] |
Scn1a +/− [13] | A voltage-gated sodium channel NaV1.1 as a primary sodium channel specifically in GABAergic neurons | Hyperactive [13] | Decreased sIPSC and increased sEPSC frequency in the hippocampus and prefrontal cortex [13] |  | |
Cntnap2 −/− [28] | A kind of neurexin family, implicated in neuron-glia interactions and K+ cahnnel clustering [28] | Hyperactive [28] | Decreased GABAergic neurons in the corpus callosum, somatosensory cortex, and striatum [28] | Repetitive self-grooming with a D2R antagonist, risperidone [28] | |
NRXN1α −/− [86] | A presynaptic protein that binds to postsynaptic protein, neuroligin, forming and strengthening synapses | Hypoactive [87] | Decreased mEPSC frequency in the hippocampus [86] |  | |
Expression of dominant negative mutation of neurexin 1β [88] |  | Decreased mEPSC and mIPSC frequency in the somatosensory cortex [88] |  | ||
Shank3b −/− [34] | A scaffolding and postsynaptic density (PSD) protein found at glutamatergic synapses, forming complexes with PSD95, SAPAP, Homer, and GKAP Implicated in 22q13 deletion syndrome (Phelan–McDermid syndrome), | Self-injurious grooming Decreased rearing [34] | Decreased cortico-striatal pop-spike amplitude [34] |  | |
En2 −/− [89] | A transcription factor which is important for development, including neuronal differentiation of the mid/hind brain [90] | Hyperactive (only p21–27) [89] | Decreased GABAergic neurons in the hippocampus and cerebral cortex [90] |  | |
Ephrin-A −/− Ephrin-A3 −/− [91] | A ligand of cell-surface ephrin receptor implicated in development and synaptic plasticity of neurons [92, 93] | Self-injurious grooming Hypoactive Decreased rearing [91] | ` |  | |
Shank1 −/− [94] | A scaffolding and PSD protein found at glutamatergic synapses, forming complexes with PSD95, SAPAP, Homer, and GKAP | Hypoactive Impaired rotarod performance [94] | Smaller dendrites and thinner PSDs in hippocampal neurons Decreased mEPSC in the hippocampus Decreased input–output (I/O) curve in the hippocampus [94] |  | |
Eif4ebp2 −/− [95] | Initiation of translation by leading eukaryotic mRNA to ribosomes |  | Increased mEPSC amplitude and frequency Increased mIPSC amplitude Increased net E/I ratio in the hippocampus [95] |  | |
Viaat (vesicular inhibitory amino acid transporter)-Mecp2 −/y [96] | Suppression or activation of target genes and implicated in Rett syndrome | Hypoactive [96] | Decreased mIPSC amplitude in cortical slices Impaired LTP in the hippocampus Mecp2 depletion in inhibitory neurons [96] |  | |
Jumping | C58/J [32] | Â | Â | Repetitive jumping with a mGluR5 negative allosteric modulator, GRN-529 [25] | |
Shank2 −/− [12] | A scaffolding and PSD protein found at glutamatergic synapses, forming complexes with PSD95, SAPAP, Homer, and GKAP | Hyperactive Decreased digging [12] | Decreased NMDA/AMPA ratio Impaired LTP and LTD in the hippocampus [12] |  | |
NL2 overexpression [79] | An adhesion molecule binding with presynaptic neurexins, regulating excitatory and inhibitory synaptic functions | Â | Enlarged synaptic contact size Increased mIPSC frequency in PFC Decreased E/I balance in PFC [79] | Â | |
Circling | Scn1a +/− [13] |  | Hyperactive [13] | Decreased sIPSC and increased sEPSC frequency in the hippocampus and prefrontal cortex [13] |  |
Gabrb3 −/− [97] | A subunit of GABA-R, a chloride channel, implicated in ASD and seizure | Decreased rearing [97] | Hypoplasia of the cerebellar [97] |  | |
Decreased marble burying | Shank1 −/− [39] |  | Decreased rearing [39] |  |  |
Ephrin-A −/− Ephrin-A3 −/− [91] | A ligand of cell-surface ephrin receptor implicated in development and synaptic plasticity of neurons [92, 93] | Self-injurious grooming Hypoactive Decreased rearing [91] | ` |  | |
C58/J) [32] | Â | Hyperactive | Â | Â | |
Glutamate receptor, ionotropic, N-methyl D-aspartate 1 (Grin1) knock-down [11] | An NMDA-R subunit implicated in synaptic plasticity | Hyperactive Decreased anxiety [72] | Â | Â | |
Increased marble burying | BTBR [16] | Â | Hyperactive | Decreased sIPSC and increased sEPSC frequency in the hippocampus [27] No corpus callosum [24] | Â |
Eif4ebp2 −/− [95] | Initiation of translation by leading eukaryotic mRNA to ribosomes |  | Increased mEPSC amplitude and frequency Increased mIPSC amplitude Increased net E/I ratio in the hippocampus [95] |  | |
FMR1 −/− [98] | Regulation of hundreds of mRNAs in the synapses Depletion of FMR1 leads to fragile X syndrome | Hyperactive [99] | Hyper-excitability caused by decreased activities of fast-spiking (FS) inhibitory neurons in the somatosensory, barrel cortex. [100] |  | |
Rearing | C58/J [32] | Â | Â | Â | |
Head poking | Shank3 −/− [101] |  | Hypoactive [101] | Increased spine length in the hippocampus Decreased mIPSC frequency and Impaired LTP in the hippocampus [101] |  |
Forelimb movements | Expression of truncated Mecp2 [102] | Suppression or activation of target genes and implicated in Rett syndrome | Hypoactive Motor deficits [102] | Â | Â |
Viaat-Mecp2 −/y [96] |  | Decreased mIPSC amplitude in cortical slices Impaired LTP in the hippocampus Mecp2 depletion in inhibitory neurons [96] |  | ||
Hanging | Expression of SERT Ala56 [103] | Returns serotonin excreted into the synaptic cleft to the presynaptic boutons | Â | Decreased firing in dorsal raphe neurons Hyperserotonemia [103] | Â |