Mouse Genome Informatics
hm1
    Park2tm1Roo/Park2tm1Roo
either: 129S2/SvPas or (involves: 129S2/SvPas * C57BL/6)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• reduced amphetamine-induced motor activity

growth/size/body
• reduced body weight after weaning, both males and females

homeostasis/metabolism
• reduced rectal temperature relative to wild-type
• increased in the limbic brain areas
• increased levels of the MAO-derived metabolite, DOPAC, relative to COMT-derived metabolite, 3-MT, indicating an impairment of dopamine release

muscle
N
• no evidence of muscle degeneration (J:85561)

nervous system
N
• brain morphology, weight, and size were normal (J:85561)
• increased in the limbic brain areas
• increased levels of the MAO-derived metabolite, DOPAC, relative to COMT-derived metabolite, 3-MT, indicating an impairment of dopamine release
• inhibition of dopamine neurotransmission
• inhibition of glutamate neurotransmission
• normal levels of 5-HT and 5-HIAA in the striatum, limbic system, diencephalon, and brainstem

Mouse Models of Human Disease
OMIM IDRef(s)
Parkinson Disease 2, Autosomal Recessive Juvenile; PARK2 600116 J:85561


Mouse Genome Informatics
hm2
    Park2tm1Roo/Park2tm1Roo
involves: 129S2/SvPas
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• null mice have increased mortality risk, displaying early onset of mortality and more rapid decline after 12 months of age

behavior/neurological
• aged mice show dyskinesia and a tendency to reduced mobility
• significant shortening of hind-limb stride length relative to controls
• mutants display dystonic tails

nervous system
• aged mice show reduction in area of substantia nigra
• in aged mice, soluble and sarkosyl insoluble tau levels are increased 200% in striatum compared to age-matched controls; tau levels are elevated in cerebral cortex
• tau immunoreactive clusters of dystrophic neurites are increased in hippocampi of 22-month old null animals
• in cultured neurons from aged mice, tau accumulation in neuritic varicosities and perinuclear areas results in disruption of neuronal axons; tau accumulation is higher than in wild-type
• ~35% loss of dopaminergic (tyrosine hydroxylase +ve) neurons in substantia nigra relative to controls or young Park2-null mice
• cortical neuron degeneration is observed in aged mice
• seen in aged mice

respiratory system
• postural abnormalities cause respiratory problems

skeleton
• dorsal kyphosis

integument
• focal alopecia observed in aged mice

cellular

Mouse Models of Human Disease
OMIM IDRef(s)
Parkinson Disease 2, Autosomal Recessive Juvenile; PARK2 600116 J:125148


Mouse Genome Informatics
cn3
    Gt(ROSA)26Sortm1Lrsn/Gt(ROSA)26Sor+
Park2tm1Roo/Park2tm1Roo
Slc6a3tm1(cre)Lrsn/Slc6a3+
Tfamtm1Lrsn/Tfamtm1Lrsn

involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• YFP+ neurons exhibit one or more grossly enlarged, rounded mitochondria in the perinuclear region of the soma and in proximal segment of dendrites with some cells containing fragmented mitochondria and small, spherical mitochondrial clustered around the nucleus
• YFP+ neurons exhibit a progressive reduction in distal axonal mitochondrial numbers compared with control cells
• however, mitochondria in the distal dopamine axons are morphologically spared
• neurons exhibit less intense staining with a retrograde tracer (fluorogold) suggesting impaired retrograde transport and/or uptake of the tracer compared with control cells