Schizophrenia Research Forum: Animal Models

Name	DA-related behavior	Gating	Cognitive behavior	Social behavior	Molecular morphological signature	Response to APD
Alpha-CaMKII KO, Heterozygous	Increased locomotor.		Deficits in working memory.	Increased aggressive behavior.	Impaired neuronal development in the dentate gyrus.
Calcineurin Agamma KO	Enhanced response to amphetamine	Disrupted PPI and latent inhibition	Disrupted PPI and latent inhibition	Impaired social interaction	Inducible KO
Cannabinoid Receptor 1 (CB1) KO	Decreased PCP-induced locomotion			No effect on social interaction
Catecholamine O-methyl transferase (COMT) KO	No potentiation of amphetamine-induced locomotion		Impaired recognition memory in heterozygous only	No deficit in sociability or social novelty in KO or hets	Increased DOPAC, D1 and D2 unchanged	Increased anxiety and aggression
Chakragati Mouse (ckr)	Circling, hyperactive	PPI and latent inhibition deficits		Reduced social interactions	Enlarged ventricles
Chromosome 22 Deletion		Disrupted PPI	Impaired cognitive function
Complexin I KO	Decreased amphetamine-induced locomotion		No cognitive deficits in two-choice swim tank	Social deficits; no preference for social novelty; no aggressive behavior in resident-intruder paradigm
Complexin II KO			Decreased LTP; reduced Morris water maze performance only after stress
DBA/2 Mouse		Disrupted N40 gating and PPI			Decreased levels Glu, tau and GABA in hippocampus	Phenotype reversed by a7-nicotinic and α4β2 receptor agonist; by olanzapine via alpha7-nicotinic receptor; by gestational choline supplementation; by baclofen and clozapine
DISC 129S6/SvEv Mouse			Working memory deficit		DISC1 mutation; deficit in hippocampal short term plasticity; altered organization of neurons in dentate gyrus
DISC1 KO	Enhanced locomotor activity	Disrupted PPI; Decreased latent inhibition		Impaired social interaction	Decreased cortical parvalbumin-containing cells, accelerated neurogenesis with aberrant connectivity
Disc1tr (Truncated) Mouse	Increased immobility	Impaired conditioning of latent inhibition			Enlarged ventricles; reduced parvalbumin neurons in hippocampus and mPFC
Disheveled 1 KO		Disrupted PPI		Impaired social interaction
Dopamine Transporter KO	Increased DA and decreased D1R, D2R, hyperactive	Disrupted PPI	Impaired adaption to environmental changes in Morris water maze	Impaired social behavior	Decreased LTD in hippocampus	More aggressive; impairments in Morris water maze reversed by haloperidol and acute nicotine treatment; LTD reversed by haloperidol
Dysbindin-1, Sandy (sdy) Mouse	Delayed hyperactivity in novel environment; less active in open field		Object recognition deficit; impaired long-term memory retention and working memory	Decreased social interaction	DTNBP1 mutation with lack of dysbindin protein; increase in DA metabolism in different brain regions; reduced snapin in hippocampus; decreased DA levels in cortex, hippocampus and hypothalamus; altered kinetics of transmitter release
ErbB4 KO	Reduced spontaneous activity; hyperactivity in open field		Reduced Morris water maze learning		Reduced myelination, enhanced DA receptor expression
FEZ1 KO	Hyperactive; enhanced response to MK-801 and methamphetamine				Increased methamphetamine-induced DA release in nucleus accumbens
GABAAalpha3 Receptor KO	Spontaneous locomotor activity slightly increased but not after amphetamine	Disrupted PPI				PPI defect improved by haloperidol Rx
Galphas Overexpression in Forebrain	Hyperlocomotion	PPI deficit	Impaired hippocampus-dependent learning and memory retrieval		Enlarged ventricles	PPI deficits reversed by haloperidol and rolipram
GAP-43 KO	Hyperactive in open field, reduced anxiety	Disrupted PPI
GDI1 Knockout			Impaired short-term memory	Diminished social behavior		Less aggression
Heterozygous Nurr1 KO	Hyperactive in novel environment and also after amphetamine		Decreased emotional memory		Reduced DA turnover in striatum; Increased DA turnover in PFC	Haloperidol reverses spontaneous hyperactivity
Heterozygous Reeler Mouse	Enhanced mesolimbic dopamine	Cross-modal PPI deficits, no unimodal PPI deficit	Decreased working memory; no decrease in prefrontal cortex dependent task	Impaired social interaction	Reduced GAD 67, increased DNA methylation; increased truncated TrkB receptor, decreased BDNF/TrkB signaling in frontal cortex
Homer1a KO	Enhanced locomotor behavior to MK-801 and methamphet-amine	Disrupted PPI	Decreased radial arm maze performance		Decreased glutamate release in PFC following cocaine Rx
Inducible Mutant hDISC1 Mice	Spontaneous hyperactivity		Deficient spatial memory in females	Alterations in social interaction	Attenuation of neurite outgrowth in cortical neurons; enlarged ventricles
Insulin Receptor KO		Decreased startle amplitude			Decreased insulin receptor and Akt signaling; reduced phosphorylated GSK-3	Clozapine alleviates insulin resistance
MCH KO Mice	Increased basal locomotor activity; hypersensitive locomotor response to d-amphetamine
mGluR1 Knockout		Disrupted PPI				Not reversed by raclopride
mGluR5 Knockout	Abnormal locomotor patterns; increased sensitivity to hyperlocomotive effects of MK-801	Disrupted PPI	Short term spatial memory deficits			APD not effective; clozapine reversed PPI deficit and ameliorated locomotor disruption (Gray)
NCAM-180 KO		Disrupted PPI, no changes induced by apomorphine Rx				Increase lateral ventricle size
Neuregulin 1 Hypomorph (Transmembrane Domain)	Hyperactive in open field test	Disrupted PPI	No impairment in spatial learning or working memory but diminished social recognition memory	Increase in dominance related and aggressive behavior depending on environment	Reduced NMDA receptor activity; increased serotonin 2A receptors and serotonin transporters in CNS	Open field behavior reversed by clozapine but not PPI
Neurexophillin 3 KO	Reduced rotorod performance	Disrupted PPI but increased startle response			Expressed in Cajal-Retzius cells
NgR1 KO	Mildly hypoactive	Strain-background dependent absence of PPI	Reduced spatial working memory
NMDA NR1 Receptor Hypomorph	Enhanced response to amphetamine	Disrupted PPI		Impaired social interaction	95% reduction in NR1 expression	Behaviors improved by APD
nPAS 1/3 KO	Enhanced open field locomotion	Disrupted PPI	Decreased social recognition		Reduced reelin interneurons
Oxytocin and Oxytocin Receptor KO		PCP treatment induces large deficits in PPI		Impaired social discrimination		More aggressive
Trace Amine 1 Receptor KO	Enhanced locomotor response to amphetamine	Disrupted PPI			Increased psychostimulant-induced DA release
Transient D2 Receptor Overexpression	Hyperactive		Impaired working memory		Overexpression of D2 receptors in striatum
Type III Nrg1 Targeted Disruption, Heterozygous		PPI deficits	Impaired short-term memory		Enlarged ventricles; decreased dendritic spine density on subicular neurons	PPI deficits reversed by chronic nicotine treatment
Prefrontal Cortical Lesion	Lesion potentiation of amphetamine induced locomotion under high stress conditions only	Medial lesions only augment PPI and lesions have no effect on LI
GLAST (EAAT1) KO	Locomotor hyperactivity in novel environment; exaggerated hyperactivity in response to MK-801					Phenotype normalized by haloperidol and mGlu2/3 agonist
YWHAE Heterozygous KO	Normal activity in open field	No PPI deficits	Mild deficit in spatial working memory, no impairment in reversal learning	Normal social interaction	50% reduction of 14-3-3epsilon protein expression
SNAP 25 overexpression	Normal locomotion in open field	No PPI deficit	Impaired spatial learning in water maze; impaired contextual fear conditioning		Overexpression of SNAP 25 in hippocampus of adult rat
Serine Racemase 1st exon KO	Hyperactive		Impaired spatial memory; disrupted order of events representation	No social interaction deficit	Lack ability to produce D-Serine; altered glutamatergic neurotransmission; abnormal dendritic morphology
Brattleboro (vasopressin-deficient) rats	Hyperactive in novel setting	Increased acoustic startle and decreased PPI		Impaired social discrimination	Point mutation in gene for vasopressin; decreased dopamine concentration in frontal cortex	PPI deficit reversed by acute clozapine and risperidone; chronic but not acute haloperidol reverses deficit
Nurr1 Heterozygous KO	Hyperactive in novel environment and also after amphetamine; enhanced response to MK-801	Disrupted PPI in males but not females	Decreased emotional memory; intact spatial memory	No social interaction deficit	Reduced DA turnover in striatum; Increased DA turnover in PFC	Haloperidol reverses spontaneous hyperactivity
Vasopressin 1a receptor KO			Decreased social recognition			Phenotype rescued by increase V1a expression in lateral septum
Vasopressin 1b receptor KO	Reduced PFC DA	Disrupted PPI	Impaired novel object recognition	Decreased social interest; decreased social novelty preference; Impaired social recognition		Atypical APD improve PPI but not haloperidol
AKT1 KO Mice	Normal activity in open field	No baseline PPI in males, baseline PPI deficit in females (Chen; Emamian did not find PPI deficit in either sex at baseline); PPI deficit caused by amphetamine	No impairment in spatial learning			Antipsychotics did not normalize PPI in females, but GSK inhibitors did
Cannabinoid receptor 2 KO	Hypoactive in open field; enhanced hyperactivity in response to cocaine	PPI deficit	Impaired memory consolidation			PPI deficit improved by risperidone
Homer1 KO	Hypoactive; enhanced locomotor behavior to MK-801 and methamphetamine	Disrupted PPI (Szumlinski; not found by Jaubert)	Decreased radial arm maze performance	Increased social interaction; increased aggression in heterozygotes; impaired nest-building	Decreased glutamate release in PFC following cocaine Rx
Neurotensin-2 receptor KO mice	Hyperactive in open field (Liang; – not found by Feifel)	Enhanced PPI in males			Increased striatal dopamine
Nitric oxide synthase KO mice	Hyperactive in novel setting	No PPI deficit	Impaired spatial memory; impaired contextual fear conditioning	Increased social interaction; reduced social novelty preference
Nogo-A KO mice	Enhanced hyperactivity in response to amphetamines	PPI deficit	Perseverative behavior; normal spatial learning
P35 (CDK5 Activator) Heterozygous Knockout Mice	No locomotor abnormalities	PPI deficit in females, not males	Reversal learning impaired in females	Social interaction deficit in males
PACAP KO Mice	Hyperactive in open field	PPI deficit		Reduced social interaction		Hyperactivity reduced with risperidone; PPI deficit reversed by risperidone; social interaction deficit and hyperactivity reduced when animals raised in enriched environment
PDGFR-beta KO mice		PPI deficit	Impairment in fear conditioning	Decreased social interaction	Reduced GABAergic neurons in HPC, PFC and amygdala
PGE2 EP2 KO mice	Normal activity in open field	PPI deficit	Normal spatial memory; impaired fear conditioning	Impairment in social habituation
Urokinase Plasminogen Activator Receptor KO (Plaur Mice)			Impaired reversal learning		Reduced parvalbumin-positive interneurons in anterior cingulate and orbitofrontal cortex; reduced levels of HGF/SF	Postnatal supplementation with HGF/SF normalizes reversal learning impairment
Rictor KO mice		PPI deficit			Reduced phosphorylation of AKT1; reduced dopamine in frontal cortex
RIM1alpha KO mice	Hyperactive in novel setting; enhanced response to MK-801	PPI deficits		Decreased social interaction
Sp4 Hypomorphic Mice		PPI deficit	Impaired spatial learning; impaired LTP		Hippocampal vacuolization; abnormal development of dentate gyrus; reduced levels of NMDA-NR1 but not NR2A or NR2B
Synapsin III KO mice	Hyperactivity in open field	PPI deficit	Normal spatial learning; object recognition deficit; Abnormal fear conditioning
Tcf4 Overexpressing Transgenic Mice	Normal activity in open field	PPI deficit	Normal spatial learning in water maze task; impaired fear conditioning
DISC 129S6/SvEv Mouse (25-bp deletion in exon 6)			Working memory deficit		DISC1 mutation; deficit in hippocampal short term plasticity; altered organization of neurons in dentate gyrus
DISC1 mutant (exon 2/3 deletion)	Normal activity in open field	PPI deficit	No impairment in working memory or novel object recognition	Increased social interaction	No morphological changes; altered threshold for LTP
Transient DISC1 Knockdown in PFC in utero	Normal spontaneous locomotion; hypersensitive to methamphetamine	PPI deficits in adults but not juveniles	Impairment in novel object recognition test		Reduced dopamine concentration in PFC; Reduced parvalbumin-positive interneurons in PFC	PPI deficits normalized by clozapine; impairment in novel object recogntion test normalized by clozapine
Chromosome 22q11.2 deletion-Df1 mice		Disrupted PPI	Impaired cognitive function		Haploinsufficiency of Tbx1 and Gnb1l responsible for PPI deficit
Chromosome 22q11.2 Deletion Model-Lgde1 Mice	Normal activity in open field	PPI deficit	Normal fear conditioning		Disrupted cortical neurogenesis and interneuron migration
Chromosome 22q11.2 Deletion Model-Df(16)A Mice	Hyperactive in novel environment	PPI deficit	Impaired fear conditioning; spatial learning deficit		Reduced dendritic spines in HPC; reduced hippocampal-prefrontal synchrony
Glycine Transporter KO	Locomotor response to psycho-stimulants same as wild-type	Reduced sensitivity to amphetamine to disrupt PPI but more MK-801 induced disruption	Improves memory retention		Increased NMDA receptor expression and function
Grin1D481N		Persistent latent inhibition	Spatial recognition impairments	Social approach deficits	Reduced NMDAR glycine affinity	Phenotype reversed by D-serine treatment
GSK-3beta Knockout		Disrupted PPI correlates with enzyme activity; no PPI disruption (Bersudsky)
Heterozygous Tbx1 and Gnb1 KO		Reduced PPI
Neurotensin-1 receptor KO mice	Hyperactive in open field; no effect of PCP on locomotor activity; enhanced hyperactivity in response to amphetamine	No PPI deficit (Feifel)			Decreased glutamate and NMDA-2A subunit concentration; increased striatal dopamine
Adenosine Kinase Transgenic Mice	Reduced locomotor response to amphetamine; enhanced locomotor response to MK-801		Learning deficits in Morris water maze and Pavlovian conditioning		Overexpression of adenosine kinase; reduced levels of adenosine in brain
AMPAR GluR1 Subunit KO	Hyperactive, no effect of MK-801 on locomotor behavior	PPI deficit	Disrupted spatial working memory	Disorganized social behaviors	Slowed extracellular DA clearance in striatum	Anxiety prone; Hyperactivity reversed by haloperidol
Aph1B/C KO	Enhanced hyperactivity in response to amphetamine	PPI deficits, hypersensitive to MK-801 (increased PPI deficits)	Impaired working memory on Morris water maze		Enhanced DA turnover in ventral striatum; gamma-secretase dependent cleavage of Nrg1 is impaired	Haloperidol and clozapine reverse PPI deficits
Apomorphine Susceptible Rat	Enhanced locomotor response to novel open field	Disrupted PPI and diminished latent inhibition; Visual and acoustic PPI deficits; Sprague-Dawley rats more sensitive t			Preferential mobilization of NMDAR NR1 subunits in D1R containing neurons of the nucleus accumbens
BACE1 KO	Increased novelty-induced hyperactivity; hypersensitivity to locomotor effects of MK-801	PPI deficits	Working memory deficits; impaired in inhibitory avoidance task	Alterations in social recognition	Impaired processing of NRG1; decreased spine density and mature spines in CA1	Clozapine attenuates novelty-induced hyperactivity and normalizes PPI deficits
PDE4B KO	Reduced baseline motor activity; exaggerated locomotor response to amphetamine	Decreased PPI	No deficit in Morris water maze		Decreased striatal DA and 5-HT activity
Phosphodiesterase 1B KO	Enhanced behavioral response to methamphetamine		Morris water maze performance impairment		Increased DARPP-32 phosphorylation
PLC-beta1 KO	Hyperactive	Sensorimotor gating deficits	Memory impairment and lack of acquisition on hippocampal-dependent fear conditioning task	Abnormal social behavior		Clozapine (McOmish) and haloperidol (Koh) rescues sensorimotor deficits
Proline Dehydrogenase (ProDH) KO	Reduced open-field behavior, enhanced response to amphetamine and MK801	Diminished PPI			COMT, calcineurin upregulation, reduced D1 and DARPP-32 expression
Regulator of G-protein Signaling 4 (RGS4) KO		Subtle PPI deficits	Impaired working memory
Retinoic Acid Receptor KO	Reduced open field locomotion				Reduced D1R and D2R
Selectively Bred Low PPI Wistar Rats	Reduced motivation	PPI deficits, reduced startle habituation	Enhanced perseverative behavior	Decreased social interaction
Serine Racemase Targeted Disruption	Hyperactive		Impaired spatial memory		Lack ability to produce D-Serine; altered glutamatergic neurotransmission
SNAP 25 Mutant Mouse	Deficit in exploratory behavior	PPI deficit		No social interaction deficit
SREB2 Transgenic Mice		PPI impairments	Contextual memory deficits in fear-conditioning task	Decreased social interaction	Overexpression of SREB2 (GPCR85) in forebrain; Reduced brain weight, increased ventricular volume
STOP KO	Hyperactive; alterations in dopaminergic neurotransmission in the mesolimbic pathway	Disrupted PPI	Deficits in short term memory and spatial learning; deficits in long-term memory and object recognition	Deficits in social learning and recognition	Enlarged ventricles; reduced volume of cortex and diencephalon; hypoglutamatergic activity	PPI deficit not blocked by clozapine
Synapsin II KO		PPI deficit		Social interaction deficit
SynGAP Heterozygote	Hyperactive; increased stereotype in open field	Increased acoustic startle response; reduced PPI	Apparent working memory impairment in T-maze alternation task; Decreased fear conditioning	Impaired social memory; deficit in social interaction		Clozapine improves hyperactivity
Neuregulin-1 Heterozygous Knockout Of EGF-Like Domain Mice	Hyperactive in open field (Duffy; not replicated by Ehrlichman or Moy); normal exploratory behavior	No PPI deficit	Normal novel object exploration	Decreased social interaction (Ehrlichman; increased sociability but decreased social novelty preference found by Moy)
Neuregulin-1 Type II Hypomorphic Rats	Normal activity in open field; impaired habituation in males, enhanced habituation in females	Enhanced habituation; PPI deficit in females			Increased basal corticosterone levels
Neuregulin-1 Heterozygous Knockout Of Ig-Like Domain Mice	Normal activity in open field		Impaired latent inhibition			Clozapine reduced activity in open field
Neuregulin-1 Overexpression In Mice	Hyperactive in novel setting (Kato; not found by Deakin); impaired performance on rotarod	Increased startle response and PPI deficits (Deakin, not found by Kato)	Impaired context-dependent fear conditioning	Impaired nest-building; decreased social interaction, increased aggression
Erb2/4 CNS KO Mice	Normal locomotor behavior	PPI deficit in males only		Increased aggression	Reduced dendritic spine density	Clozapine reduced behavioral changes
Grin1D481N NR1 Point Mutation		Persistent latent inhibition; no PPI deficit; increased startle reactivity	Spatial recognition impairments	Social approach deficits	Reduced NMDAR glycine affinity; reduced LTP in hippocampus	Phenotype reversed by D-serine treatment as well as D-amino acid oxidase gene deletion
Combined Grin D481N/K483Q Point Mutation	Nonhabituating hyperactivity	Increased startle response, no PPI deficit	Impaired spatial learning	Impaired nest building	Reduced NMDAR glycine affinity; reduced LTP in hippocampus	Clozapine and haloperidol did not reduce hyperactivity
Disc1tr (truncated, exons 1-8) Mouse	Increased immobility	Impaired conditioning of latent inhibition			Enlarged ventricles; reduced Parvalbumin neurons in hippocampus & mPFC
DISC1 Dominant-Negative Transgenic Mice	Hyperactive in open field	No PPI deficit	No impairment in working memory in T-maze or spatial learning in water maze	Impaired social interaction	Decreased cortical parvalbumin-containing cells
DISC1 L100P Missense Mutation	Increased locomotor activity; enhanced response to amphetamine	Disrupted PPI; Decreased startle amplitude	Working memory impaired in T-maze; normal spatial learning in water maze		Reduced brain volume; reduced dendritic spine density; increased striatal dopamine receptors	Clozapine and haloperidol reversed PPI deficit; genetic inactivation of GSK-3alpha improves PPI, hyperactivity and dendritic spine abnormalities
AMPA GluR4 KO mice	Normal activity in open field; increased sensitivity to MK-801	Reduced startle response; PPI deficits	Impaired spatial learning, but enhanced performance in reversal learning	Increased social interaction with familiar cagemate
NCAM-EC overexpressing mice	Hyperactive in open field; enhanced response to amphetamine and MK-801	PPI deficit	Decreased LTP in PFC, normal LTP in HPC; impaired working memory	Normal sociability	Abnormal GABAergic interneurons	PPI deficit reversed by clozapine but not haloperidol
Beta-arrestin 2 KO	Decreased locomotor response to amphetamine				Normal DARRPP-32 phosphorylation after amphetamine
D-Amino Acid Oxidase Deficient Mice-ddy/DAO Strain	Hypoactive in open field; attenuated response to PCP	Increased startle amplitude; no PPI deficit (Almond; enhanced PPI found by Zhang)
Densin-180 (LRRC7) KO mice	Hypoactive in familiar setting; hyperactive in novel setting	PPI deficits	Impaired spatial memory; Impaired novel object recognition	Impaired nest-building; increased aggression	Impaired LTD; altered morphology of dendritic spines
FGFR1 Catecholaminergic Neuron Targeted Knockout Mice	Hyperactive in open field	Increased startle response; PPI deficits		Decreased social interaction	Increased striatal dopamine metabolites	PPI deficit reversed with flupenthixol, quetiapine and clozapine; clozapine did not reduce hyperactivity
Fut8 (alpha1,6-fucosyltransferase) KO Mice	Hyperactive in novel setting	PPI deficit	Impaired working memory	Decreased social interaction		Hyperactivity reduced by haloperidol
Glutamate-Cysteine-Ligase Modifier (GCLM) KO Mice	Hyperactive in novel setting (Kulak; not found by Cole); potentiated locomotor response to amphetamine	No PPI deficits (Cole); mild PPI deficit (Kulak)	Normal spatial working memory and spatial learning	Abnormal social preference (Kulak)	Glutathione deficiency
Glutamate Carboxypeptidase II (GCP II) Heterozygous KO Mice	Hyperactive in open field	No PPI deficit	Mild impairment in spatial working memory	Decreased social interaction
HB-EGF Forebrain-Specific KO Mice	Hyperactive in novel setting and home cage	PPI deficits	Impaired novel object recognition	Decreased social interaction	Reduced dopamine, serotonin, PSD-95 and NR1 in prefrontal cortex	Hyperactivity reduced by haloperidol and clozapine; PPI deficits reduced by risperidone and clozapine; clozapine but not haloperidol improved social behavior
Imprinting Center Deletion Model Of PWS	Hypoactive in open field	Increased acoustic startle; PPI deficit	Impaired attention in serial reaction time task
LPA1 Receptor KO mice	Reduced activity in novel setting; impaired habituation	PPI deficit	Impaired spatial working and reference memory		Abnormal expression and phosphorylation of NMDA and AMPA subunits
LRRTM1 KO Mice	Hypoactive in novel settings		Deficit in spatial memory in water maze task	Deficit in social recognition	Reduced hippocampal volume and synaptic density
Midkine (Mdk) KO Mice	Normal activity in open field	PPI deficit	Normal novel object recognition	Decreased social contacts, but increased time per contact	Reduced dopamine, D1R and D2R in striatum
Neuropeptide Y Receptor 1 (Y1) KO mice		Reduced startle response; impaired habituation; no PPI deficit
Neuropeptide Y Receptor 2 (Y2) Knockout mice	Hyperactive in open field	PPI in males	Normal working memory and reference memory	Increased social interaction in males