Phenotypes Associated with This Genotype

Genotype
MGI:5316006

• Allelic Composition: Slc6a3^tm2(tTA)Xz/Slc6a3⁺; Tg(tetO-COX8A/PstI*)1Ctm/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * C57BL/6J * SJL

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

behavior/neurological

decreased exploration in new environment ( J:178139 )

• mutants at 2 months of age exhibit a decrease in the exploration time in the activity cage, with this reduction lasting the duration of the dark cycle

impaired coordination ( J:178139 )

• at 4 months of age, mutants exhibit an increased latency time to descend a pole from a fixed height, indicating poor motor coordination

• however, mutants show normal rotarod performance

• 4 month of mutants treated with L-DOPA and carbidopa, a common therapy for Parkinson Disease, exhibit improved performance on the pole test and the activity cage

growth/size/body

slow postnatal weight gain ( J:178139 )

• mutants gain weight at a slower rate than controls; this slower weight gain is first observed at 2 months of age

homeostasis/metabolism

decreased dopamine level ( J:178139 )

• mutants show a significant reduction in overall all amount of dopamine at both 4 and 12 months of age compared to controls

• mutants however show an increase in the amount of HVA and DOPA, downstream metabolites of dopamine, indicating altered dopamine metabolism in the striatum

abnormal noradrenaline level ( J:178139 )

• mutants over 12 months of age exhibit an increase in monoamine neurotransmitters, noradrenaline and serotonin

increased serotonin level ( J:178139 )

• mutants over 12 months of age exhibit an increase in monoamine neurotransmitters, noradrenaline and serotonin

nervous system

abnormal substantia nigra morphology ( J:178139 )

• at 9 months of age, but not 4 months, mutants exhibit a 60% reduction in TH+ neurons in the substantia nigra, and by 12 months of age, very few TH+ neurons are left in the substantia nigra

abnormal striatum morphology ( J:178139 )

• mutants exhibit a reduction in TH+ neurons in the striatum at 4 months of age

abnormal synaptic bouton morphology ( J:178139 )

• mutants exhibit a reduction in dopamine transporter steady-state levels in the striatum, indicating a reduction of dopaminergic presynaptic terminals in the striatum at 4 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease		DOID:14330	OMIM:PS168600	J:178139