Phenotypes associated with this allele

• Allele Symbol: Slc6a3^tm1Hhg
• Allele Name: targeted mutation 1, Howard H Gu
• Allele ID: MGI:3653596
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Slc6a3^tm1Hhg/Slc6a3^tm1Hhg	B6.129X1-Slc6a3^tm1Hhg	MGI:5318772
hm2	Slc6a3^tm1Hhg/Slc6a3^tm1Hhg	involves: 129X1/SvJ * C57BL/6J	MGI:3653646

Genotype
MGI:5318772

hm1

• Allelic Composition: Slc6a3^tm1Hhg/Slc6a3^tm1Hhg
• Genetic Background: B6.129X1-Slc6a3^tm1Hhg

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

behavior/neurological

increased locomotor activity ( J:183177 )

• in an open-field test, mutants display higher horizontal activity than controls

nervous system

abnormal CNS synaptic transmission ( J:183177 )

• sensitivity of cannabinoid CB1 receptors (CB1Rs) controlling GABA-mediated synaptic currents in the striatum is lost, however CB1Rs modulating glutamate transmission and GABAB receptors are not affected

abnormal inhibitory postsynaptic currents ( J:183177 )

• the effects of CB1R agonist HU210 on striatal neuron spontaneous inhibitory postsynaptic currents (sIPSCs) and evoked inhibitory postsynaptic currents (eIPSCs) are abolished, indicating loss of sensitivity of CB1Rs(GABA)

• however, the GABAB receptor agonist baclofen has the same effect as in controls

• cocaine or sucrose are unable to alter the HU210 effects on sIPSCs as they do in control mice

abnormal miniature inhibitory postsynaptic current frequency ( J:183177 )

• dihydroxyphenylglycine treatment does not inhibit striatal miniature inhibitory postsynaptic current (mIPSC) frequency as in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
attention deficit hyperactivity disorder		DOID:1094	OMIM:143465 OMIM:608903 OMIM:608904 OMIM:608905 OMIM:608906 OMIM:612311 OMIM:612312	J:183177

Genotype
MGI:3653646

hm2

• Allelic Composition: Slc6a3^tm1Hhg/Slc6a3^tm1Hhg
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

behavior/neurological

impaired conditioned place preference behavior ( J:111041 )

• mutants given four injections of 5 and 20 mg/kg cocaine fail to develop a conditioned placement preference compared to robust CPP in wild-type at these doses

• 2.5 mg/kg of amphetamine induces similar levels of CPP in mutants and wild-type

abnormal locomotor activation ( J:111041 )

• doses of cocaine from 10-40 mg/kg had no effect on mutants but increased activity significantly in wild-type mice; cocaine induced locomotor suppression in a dose-dependent fashion in mutants

• 10 mg/kg morphine or amphetamine stimulated locomotor activity in mutants but not in wild-type

hyperactivity ( J:111041 )

• mutants display higher baseline motor activity than wild-type

homeostasis/metabolism

increased dopamine level ( J:111041 )

• extracellular dopamine concentrations in freely-moving mice measured by microdialysis are 64% higher than in wild-type mice

nervous system

abnormal dopaminergic neuron morphology ( J:111041 )

• spontaneous firing by wild-type dopaminergic neurons in brain slices is inhibited by 53.2% by a dose of 5 um cocaine but there is no significant effect on mutant neurons

abnormal synaptic dopamine release ( J:111041 )

• amplitude of dopamine release is 25% lower and decay is 3-fold slower in mutants compared to wild-type as assessed by fast cyclic voltammetry

• release of dopamine in response to amphetamine is lower than in wild-type

abnormal neurotransmitter uptake ( J:111041 )

• in synaptosomal uptake assays, the mutant dopamine transporters are 89-fold more sensitive to cocaine inhibition than those from wild-type mice