Mouse Genome Informatics
hm1
     Slc6a3tm1Hhg/Slc6a3tm1Hhg
B6.129X1-Slc6a3tm1Hhg
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
behavior/neurological
hyperactivity ( 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 currents ( J:183177 )
• dihydroxyphenylglycine treatment does not inhibit striatal miniature inhibitory postsynaptic current (mIPSC) frequency as in wild-type mice

Mouse Models of Human Disease
 OMIM IDRef(s)
Attention Deficit-Hyperactivity Disorder; ADHD 143465 J:183177


Mouse Genome Informatics
hm2
     Slc6a3tm1Hhg/Slc6a3tm1Hhg
involves: 129X1/SvJ * C57BL/6J
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
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

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 neurotransmitter level ( J:111041 )
• extracellular dopamine concentrations in freely-moving mice measured by microdialysis are 64% higher than in wild-type mice
abnormal neurotransmitter secretion ( 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 )
• ins synaptosomal uptake assays, the mutant dopamine transporters are 89-fold more sensitive to cocaine inhibition than those from wild-type mice