Phenotypes associated with this allele

• Allele Symbol: Nr4a2^tm1Tpe
• Allele Name: targeted mutation 1, Thomas Perlmann
• Allele ID: MGI:2157566
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nr4a2^tm1Tpe/Nr4a2^tm1Tpe	involves: 129P2/OlaHsd	MGI:3723170
ht2	Nr4a2^tm1Tpe/Nr4a2^+	B6.129P2-Nr4a2^tm1Tpe	MGI:3841583
ht3	Nr4a2^tm1Tpe/Nr4a2^+	involves: 129P2/OlaHsd	MGI:3723171
cx4	Nr4a2^tm1Tpe/Nr4a2^+ Nr4a3^tm1Dgen/Nr4a3^tm1Dgen	involves: 129P2/OlaHsd	MGI:4820560

Genotype
MGI:3723170

hm1

• Allelic Composition: Nr4a2^tm1Tpe/Nr4a2^tm1Tpe
• Genetic Background: involves: 129P2/OlaHsd

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

neonatal lethality, complete penetrance ( J:39661 )

• mice die within 2 days of birth

behavior/neurological

abnormal suckling behavior ( J:39661 )

• mice appear to be unable to suckle, and at time of death, stomachs lack milk

abnormal motor capabilities/coordination/movement ( J:39661 )

• abnormal flexion-extension movements of limbs are observed

impaired righting response ( J:39661 )

• mice show difficulties in turning when placed on their backs

decreased locomotor activity ( J:39661 )

nervous system

abnormal nervous system development ( J:39661 )

• mutants fail to generate midbrain dopaminergic neurons compared to wild-type which develop dopaminergic neurons starting around E11.5

loss of dopaminergic neurons ( J:39661 )

homeostasis/metabolism

decreased dopamine level ( J:39661 )

• dopamine is absent from brains of mutants

Genotype
MGI:3841583

ht2

• Allelic Composition: Nr4a2^tm1Tpe/Nr4a2⁺
• Genetic Background: B6.129P2-Nr4a2^tm1Tpe

homeostasis/metabolism

abnormal dopamine level ( J:147544 )

• male mice exhibit a 59% dopamine decreased in the prefrontal cortex and a 38% dopamine decrease in the hippocampus compared to wild-type mice

• DOPAC levels are reduced 35% in the prefrontal cortex and 41% in the hippocampus in male mice compared to in wild-type mice

• HVA levels are reduced in the striatum in male mice compared to in wild-type mice

• female mice exhibit a 39% increase in DOPAC in the striatum and 12% in HVA compared to in wild-type mice

• male mice exhibit a 147% increase in dopamine turnover compared to in wild-type mice

• in female mice, dopamine turnover in increased in the striatum by 52% DOPAC/DA and 23% HVA/DA

• however, dopamine turnover in the prefrontal lobe in female mice is normal

abnormal noradrenaline level ( J:147544 )

• male mice exhibit a 28% increase in noradrenaline in striatum and an 11% increase in female mice in the hippocampus compared to in wild-type mice

abnormal serotonin level ( J:147544 )

• male mice exhibit a reduction in 5-HIAA in the striatum (-10%), hippocampus (-13%), and midbrain (-13%) with decreased 5-HT turnover in the striatum (-18%), hippocampus (-19%), and MB (-18%) compared to in wild-type mice

• female mice exhibit an increase in 5-HT in the midbrain (7%), 5-HIAA in the prefrontal cortex (11%), striatum (13%), and hippocampus (21%) with increased 5-HT turnover in striatum (20%), cerebellum (31%), and hippocampus (20%) compared to in wild-type mice

behavior/neurological

enhanced behavioral response to xenobiotic ( J:147544 )

• phencyclidine-treated male mice exhibit an 86% increase in locomotion and a 78% increase in motility compared to similarly treated wild-type mice

• phencyclidine-treated female mice exhibit an 134% increase in locomotion and a 87% increase in motility compared to similarly treated wild-type mice

• phencyclidine-treated female mice are more active than similarly treated male mice

• however, mice exhibit normal suppression of hyperactivity when treated with haloperidol

enhanced behavioral response to addictive substance ( J:147544 )

• male mice treated with amphetamine exhibit a 68% increase in locomotion and 64% increase in motility compared to similarly treated wild-type mice

• female mice treated with amphetamine exhibit a 90% increase in locomotion and 60% increase in motility compared to similarly treated wild-type mice

impaired passive avoidance behavior ( J:147544 )

• male mice exhibit a 45% decrease in retention latency in a passive avoidance task compared to wild-type mice

behavioral despair ( J:147544 )

• in a forced-swim test, mice exhibit increased immobility compared to wild-type mice

hyperactivity ( J:147544 )

• male mice are 82% more active and 65% more motile than wild-type mice

• female mice are 99% more active and 68% more motile than wild-type mice

• phencyclidine-treated female mice are more active than similarly treated male mice

• however, mice exhibit normal suppression of hyperactivity when treated with haloperidol

increased locomotor activity ( J:147544 )

• mice treated with amphetamine exhibit a 68% increase in locomotion and 64% increase in motility compared to similarly treated wild-type mice

• female mice treated with amphetamine exhibit a 90% increase in locomotion and 60% increase in motility compared to similarly treated wild-type mice

• phencyclidine-treated male mice exhibit an 86% increase in locomotion and a 78% increase in motility compared to similarly treated wild-type mice

• phencyclidine-treated female mice exhibit an 134% increase in locomotion and a 87% increase in motility compared to similarly treated wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
schizophrenia		DOID:5419	OMIM:181500	J:147544

Genotype
MGI:3723171

ht3

• Allelic Composition: Nr4a2^tm1Tpe/Nr4a2⁺
• Genetic Background: involves: 129P2/OlaHsd

homeostasis/metabolism

decreased dopamine level ( J:39661 )

• dopamine levels and dopamine metabolite levels are reduced in newborn heterozygotes

• adults have reduced striatal dopamine levels

Genotype
MGI:4820560

cx4

• Allelic Composition: Nr4a2^tm1Tpe/Nr4a2⁺; Nr4a3^tm1Dgen/Nr4a3^tm1Dgen
• Genetic Background: involves: 129P2/OlaHsd

nervous system

increased susceptibility to neuronal excitotoxicity ( J:162076 )

• kainic-acid treated mice exhibit decreased cell density in the CA1 hippocampus with evidence of increased oxidative stress compared with similarly treated wild-type mice

cellular

increased susceptibility to neuronal excitotoxicity ( J:162076 )

• kainic-acid treated mice exhibit decreased cell density in the CA1 hippocampus with evidence of increased oxidative stress compared with similarly treated wild-type mice

oxidative stress ( J:162076 )

• kainic-acid treated mice exhibit decreased cell density in the CA1 hippocampus with evidence of increased oxidative stress compared with similarly treated wild-type mice

homeostasis/metabolism

increased susceptibility to neuronal excitotoxicity ( J:162076 )

• kainic-acid treated mice exhibit decreased cell density in the CA1 hippocampus with evidence of increased oxidative stress compared with similarly treated wild-type mice