Mouse Genome Informatics
ht1
    Slc6a3tm2(tTA)Xz/Slc6a3tm3(tetO)Xz
involves: 129X1/SvJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• doxycyclin-treated mice exhibit reduced dopamine clearance rates compared to in wild-type mice
• 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
• 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
• doxycyclin-treated mice exhibit reduced dopamine clearance rates compared to in wild-type mice


Mouse Genome Informatics
cx2
    Slc6a3tm2(tTA)Xz/Slc6a3+
Tg(tetO-COX8A/PstI*)1Ctm/0

involves: 129X1/SvJ * C57BL/6 * C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• 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
• 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
• mutants gain weight at a slower rate than controls; this slower weight gain is first observed at 2 months of age

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

nervous system
• 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
• 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
• mutants exhibit a reduction in TH+ neurons in the striatum at 4 months of age
• 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
OMIM IDRef(s)
Parkinson Disease, Late-Onset; PD 168600 J:178139