Table 1.
DISC1 animal models.
| Mutants | Dominant negative transgenic | Knockdown | ||||||
|---|---|---|---|---|---|---|---|---|
| Constitutive | Inducible | |||||||
| Name | Q31L | L100P | Δ25 bp/stop codon | BAC-DN | CaMK-DN | CaMK-DN | CaMK-cc | In utero RNAi |
| Neurogenesis | ↓ (CTX) | ↓ (DG) | ↓ (CTX) | |||||
|
Pyramidal neurons (CTX, HP) Granule neurons (DG) |
Misposition, ↓Dendrites, ↓ Spine | Alteration | ↓ Spine | ↓Dendrite | ↓Dendrite | |||
| Interneurons (mPFC) | → PV, CB | ↓ PV | ↓ PV | ↓ PV | ↓ PV | |||
| Dopamine | ↑ D2High (STR) | ↓ DA, DOPAC (CTX) | ↓ TH, DA (CTX) | |||||
| Behavioral abnormalities | ||||||||
| Amphetamine hypersensitivity | yes | yes | yes | |||||
| MK-801 hypersensitivity | yes | |||||||
| Sensorimotor gating (PPI) | yes | yes | no | yes |
|
yes | ||
| Latent inhibition | yes | yes | yes | |||||
| Short term memory (Y maze) |
|
|
||||||
| Working memory (DNMTP) | yes | yes | yes | yes | yes | |||
| Spatial learning/memory (MWM) | no | no | no | no |
|
|||
| Fear conditioning | no | yes | ||||||
| Antidepressant-related (FST) | yes | no | yes | yes |
|
yes | no | |
| Sociability | yes | no | yes |
|
yes | |||
| Anxiety (EPM) | no | no | no |
|
no | |||
| References | Clapcote 2007, Lipina 2010, Lee 2011 |
Koike 2006 Kvajo 2008 |
Shen 2008 | Hikida 2007, Ibi 2010 | Pletnikov 2008, Ayhan 2010, Abazyan 2010 | Li 2008 | Niwa 2010 | |
The upper part describes histological and neurochemical abnormalities, studied in either the cortex or hippocampus. The lower part summarizes whether the mice display abnormalities in the indicated behavioral tests. All DISC1 animal models show substantially overlapping behavioral profiles. Two studies have combined an environmental stressor (poly I:C) with genetic risk (the putative dominant-negative C-terminal truncated human DISC1 under regulation by the CaMKII promoter)156,157. The behavioral outcome when this environmental stressor is added to the genetic model is depicted in red. CTX, cortex; DG, dentate gyrus; HP, hippocampus; mPFC, medial prefrontal cortex; STR, striatum; PV, parvalbumin; CB, calbindin; DA, dopamine; DOPAC, 3,4-Dihydroxyphenylacetic acid; TH, tyrosine hydroxylase; PPI, prepulse inhibition; DNMTP, delayed non-matching to place; MWM, Morris water maze; FST, forced swim test; and EPM, elevated plus maze. ↓, reduction; →, no change; and ↑, augmentation.