Mouse Genome Informatics
hm1
    Park2tm1Ccs/Park2tm1Ccs
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
N
• mice display normal motor skills (J:127250)
• unlike wild-type mice, exposure to amphetamine does not significantly affect behavior
• mice exhibit increased anxiety behavior in a light dark transition test in which they spend less time in the illuminated compartment and make less transitions between light and dark compartments
• mice exhibit increased thigmotaxic behavior in an open field and water maze
• unlike wild-type mice, mice do not display increased exploration on the first day in a new environment, travel less horizontal distance, and exhibit increased thigmotaxic behavior
• mice exhibit a slightly impaired spatial learning ability in a Morris water maze test in which they made fewer crossings and did not selectively cross over the hidden platform

nervous system
N
• mice exhibit normal brain morphology, and normal dopaminergic neurons, micro- and astrogliosis in the substantial nigra and locus coeruleus (J:127250)
• mice exhibit normal brain and spinal cord morphology, and normal dopaminergic neurons and axons, cell death or micro- and astrogliosis in the substantial nigra, striatum, locus coeruleus and cerebral cortex (J:127707)
• while dopamine uptake by cells is normal, monoamine metabolism of dopamine is increased in the striatum
• in old-aged mice, neurons display cytoplasmic vacuoles and disruptions in the Golgi network and endoplasmic reticulum
• in aged mice, neurons display cytoplasmic vacuoles, disruptions in the Golgi network and endoplasmic reticulum, occasionally detached outer nuclear membrane, and mitochondria abnormalities including electron dense inclusion bodies, dilated and disorganized cristae and protrusions

homeostasis/metabolism
• while dopamine uptake by cells is normal, monoamine metabolism of dopamine is increased in the striatum


Mouse Genome Informatics
hm2
    Park2tm1Ccs/Park2tm1Ccs
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• almost all mesencephalic glial cell types exhibit a higher number of structurally altered mitochondria, showing disintegration and reduction of mitochondrial cristae, mitochondrial enlargement and formation of protrusions or disruption of the outer membrane
• mitochondrial damage is noticeable at 16 days of age in all mesencephalic cell types and increases 4-8 fold in the next few weeks
• mitochondrial alterations are higher in oligodendrocytes than in astrocytes or microglia

nervous system
• almost all mesencephalic glial cell types exhibit a higher number of structurally altered mitochondria
• mitochondrial alterations are higher in oligodendrocytes than in astrocytes or microglia
• mesencephalic glial cells exhibit a higher (2.5-7-fold) percentage of damaged mitochondria than in mesencephalic neurons at 3 and 12-15 months of age

Mouse Models of Human Disease
OMIM IDRef(s)
Parkinson Disease 2, Autosomal Recessive Juvenile; PARK2 600116 J:168847


Mouse Genome Informatics
cx3
    Park2tm1Ccs/Park2tm1Ccs
Tg(CAG-SNCA*)1.1Ccs/?

involves: 129S1/Sv * 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
N
• mice exhibit normal brain and spinal cord morphology, and normal dopaminergic neurons and axons, cell death or micro- and astrogliosis in the substantial nigra, striatum, locus coeruleus and cerebral cortex (J:127707)
• in old-aged mice, neurons display cytoplasmic vacuoles and disruptions in the Golgi network and endoplasmic reticulum
• in aged mice, neurons display cytoplasmic vacuoles, disruptions in the Golgi network and endoplasmic reticulum, occasionally detached outer nuclear membrane, and mitochondria abnormalities including electron dense inclusion bodies, dilated and disorganized cristae and protrusions

cellular
• the number of damaged mitochondria is increased 195% in the substantia nigra and up to 900% in the frontal cortex compared to in wild-type mice
• however, the number of mitochondria in affected brains is normal and no mitochondrial swelling is observed
• mitochondrial damage increases and the number of mitochondria decreases with age in the substantia nigra and frontal cortex
• respiration rate is decreased 29.5% when glutamate/malate is used as a substrate after treatment with CCCP
• state 3 respiration from complex I is reduced 18.7% compared to in wild-type mice
• however, respiratory rates starting at complex II or complex III/IV or state 4 are normal


Mouse Genome Informatics
cx4
    Park2tm1Ccs/Park2tm1Ccs
Tg(Th-SNCA*)1.2Ccs/?

involves: 129S1/Sv * 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
N
• mice exhibit normal brain and spinal cord morphology, and normal dopaminergic neurons and axons, cell death or micro- and astrogliosis in the substantial nigra, striatum, locus coeruleus and cerebral cortex (J:127707)
• in old-aged mice, neurons display cytoplasmic vacuoles and disruptions in the Golgi network and endoplasmic reticulum
• in aged mice, neurons display cytoplasmic vacuoles, disruptions in the Golgi network and endoplasmic reticulum, occasionally detached outer nuclear membrane, and mitochondria abnormalities including electron dense inclusion bodies, dilated and disorganized cristae and protrusions

cellular
• mitochondrial damage increases and the number of mitochondria decreases with age in the substantia nigra
• however, the number of mitochondria in affected brains is normal and no mitochondrial swelling is observed
• the number of damaged mitochondria in the substantia nigra is increased compared to in wild-type mice
• respiration rate is decreased 23.2% when glutamate/malate is used as a substrate after treatment with CCCP
• state 3 respiration from complex I is reduced 21.0% to 29.4% compared to in wild-type mice
• however, respiratory rates starting at complex II or complex III/IV or state 4 are normal