Table 2.
Behavioral and electrophysiological features of various Cul3-KO models.
| Brain region | Model | Method | Behavior characteristics | Molecular changes | Electrophysiological characteristics |
|---|---|---|---|---|---|
| Whole brain | CRISPR/Cas9 KO mice (23) | CRISPR/Cas9 genome engineering | Hyperactivity, cognitive and social impairments. | Reduced dendritic growth, filamentous actin puncta, and spontaneous network activity. | / |
| CMV-Cre; Cul3f/+ mice (25) | Cul3f/f X CMV-Cre | ASD-like social and motor coordination deficits. | Upregulated Plastin3 leads to defects in neuronal migration. | Reduced sEPSC amplitude and frequency. | |
| Forebrain | Emx1-Cre; Cul3f/+ mice (26) | Cul3f/f X Emx1-Cre | ASD-like social and sensory-gating impairment. | Increased RhoA and spine density in mPFC; hypofunction of NMDA receptor; misregulated proteins such as Smyd3. | Reduced amplitude of NMDAR-mediated EPSC. |
| Hippocampus and cortex | NEX-Cre; Cul3f/+ mice & GFAP-Cre; Cul3f/+ mice (41) | Cul3f/f X GFAP-Cre or NEX-Cre | Social interaction deficits and anxiety-like behaviors. | Increased eIF4G1 and glutamatergic transmission, disturbed the E-I balance. | Increased mEPSC frequency and AP in CA1 neurons. |
| Basal forebrain | Chat-Cre; Cul3f/f mice (42) | Cul3f/f X Chat-Cre | ASD-like social, cognitive, sensory-gating, motor coordination deficits, and hyperlocomotion. | / | Reduced frequency of synaptically-driven AP in BF cholinergic neurons. |
| mPFC | mPFC-specific knockdown (26) | Injected AAV8-CaMKIIα-GFP-Cre into mPFC | ASD-like social deficits. | Hypofunction of NMDA receptor. | Reduced NMDAR-EPSC in mPFC pyramidal neurons. |
| Striatum | Striatum-specific knockdown (26) | Injected AAV8-CaMKIIα-GFP-Cre into the striatum | Repeat stereotyped behavior. | Attenuated neuronal excitability; decreased D1-MSN excitability. | Reduced AP firing frequency. |
| Cell culture | CUL3-KO iPSCs (60) | CRISPR/Cas9 genome engineering | / | / | Reduced neuronal excitability, but unaffected basal synaptic transmission. |
sEPSC, spontaneous excitatory postsynaptic current; mEPSC, miniature excitatory postsynaptic current; mPFC, medial prefrontal cortex; E/I balance, excitation-inhibition balance; D1-MSN, D1-dopamine receptor-expressing medium spiny neuron; AP, action potential; BF, basal forebrain.