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Phenotypes Associated with This Genotype
Genotype
MGI:5643944
Allelic
Composition
Slc6a3tm1Rbl/Slc6a3tm1Rbl
Genetic
Background
involves: 129S6/SvEvTac * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Slc6a3tm1Rbl mutation (0 available); any Slc6a3 mutation (47 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• small, but significant reduction in the expected numbers of males seen at weaning

behavior/neurological
• mice show a more robust escape response during handling termed darting, with more rapid escape responses (J:216661)
• mice show a trend toward a reduction in latency to fall in the inverted screen hang test (J:221936)
• however, mice show no deficiencies in measures of general health, motor capability, or reflexes, showing normal respiration rate, heart rate, gait, no tremors, normal performance in trunk curl, forepaw reaching, horizontal and vertical wire hanging, pole climb, rotarod, grip strength, righting reflex, air righting reflex, and ear twitch (J:221936)
• amphetamine induces a blunted (about 50%) locomotor response, in both horizontal activity and rearing, in mutants compared to wild-type mice
• methylphenidate induces blunted horizontal locomotor and vertical activity responses
• mice show a reduction in vertical activity in both number of rearing events and time spent rearing
• however, mice show normal acoustic startle responses and performance on the elevated zero maze

homeostasis/metabolism
• in vivo striatal microdialysis shows elevated basal extracellular dopamine levels
• however, mice show normal levels of dopamine, dopamine metabolites, and dopamine turnover in the striatum
• small, but significant increase in striatal and cortical, but not midbrain, serotonin levels are seen
• however, 5-hydroxyindoleacetic acid levels are normal
• in vivo striatal microdialysis shows blunted dopamine elevation in response to local and systemic amphetamine
• the amphetamine-induced increase in D2 dopamine receptor-mediated IPSC amplitude is blunted in striatal slices

nervous system
• small, but significant increase in striatal and cortical, but not midbrain, serotonin levels are seen
• however, 5-hydroxyindoleacetic acid levels are normal
• whole-cell recordings of substantia nigra dopaminergic neurons show reduced capacitance, and increased resistance
• dopaminergic neurons show alterations in basal and amphetamine-augmented D2 dopamine receptor-mediated inhibitory postsynaptic currents (IPSCs)
• the time to peak of the D2 dopamine receptor-mediated IPSC evoked by a single stimulus is increased and the duration of the IPSC evoked by a single or five stimuli is increased
• spontaneous D2 dopamine receptor-mediated inhibitory postsynaptic currents are prolonged, with no difference in amplitude
• no difference in the time to peak or duration of evoked GABA(B)-mediated IPSCs
• the amphetamine-induced increase in D2 dopamine receptor-mediated IPSC amplitude is blunted in midbrain slices
• nerve terminal dopamine release in striatal slices shows blunted amphetamine- and 4-AP-evoked dopamine release accompanied by tonic presynaptic D2 dopamine receptor stimulation


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
01/14/2020
MGI 6.14
The Jackson Laboratory