Phenotypes associated with this allele

• Allele Symbol: Slc6a3^tm2(tTA)Xz
• Allele Name: targeted mutation 2, Xiaoxi Zhuang
• Allele ID: MGI:3832286
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Slc6a3^tm2(tTA)Xz/Slc6a3^tm3(tetO)Xz	involves: 129X1/SvJ * C57BL/6J	MGI:3832324
cx2	Slc6a3^tm2(tTA)Xz/Slc6a3^+ Tg(tetO-COX8A/PstI*)1Ctm/0	involves: 129X1/SvJ * C57BL/6 * C57BL/6J * SJL	MGI:5316006

Genotype
MGI:3832324

ht1

• Allelic Composition: Slc6a3^tm2(tTA)Xz/Slc6a3^tm3(tetO)Xz
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

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

nervous system

abnormal action potential ( J:144671 )

• doxycyclin-treated mice exhibit increased overall firing rate of dopamine neurons with a high prevalence of neurons firing at rates greater than 4 Hz compared to non-treated mice

• doxycyclin-treated mice exhibit higher non-bursting firing rates than in non-treated mice

• however, burst quantity and characteristics are the same regardless of doxycyclin treatment

behavior/neurological

abnormal behavior ( J:144671 )

• doxycyclin-treated mice exhibit more lever pressing when food deprived than wild-type mice or untreated mice

• in a choice condition, doxycycline-treated mice exhibit increased lever pressing compared to wild-type mice or untreated mice

• however, in a no-choice condition mice exhibit the same amount of lever pressing as in wild-type or non-treated mice, and learning is normal

homeostasis/metabolism

increased dopamine level ( J:144671 )

• doxycyclin-treated mice exhibit reduced dopamine clearance rates compared to in wild-type mice

Genotype
MGI:5316006

cx2

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

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