Phenotypes associated with this allele

• Allele Symbol: Prkn^tm1Ccs
• Allele Name: targeted mutation 1, Christine C Stichel
• Allele ID: MGI:3764690
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Prkn^tm1Ccs/Prkn^tm1Ccs	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3764702
hm2	Prkn^tm1Ccs/Prkn^tm1Ccs	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:4939781
cx3	Prkn^tm1Ccs/Prkn^tm1Ccs Tg(CAG-SNCA*)1.1Ccs/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3764819
cx4	Prkn^tm1Ccs/Prkn^tm1Ccs Tg(Th-SNCA*)1.2Ccs/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3764820

Genotype
MGI:3764702

hm1

• Allelic Composition: Prkn^tm1Ccs/Prkn^tm1Ccs
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

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

behavior/neurological

behavior/neurological phenotype ( J:127250 )

N • mice display normal motor skills

impaired behavioral response to xenobiotic ( J:127250 )

• unlike wild-type mice, exposure to amphetamine does not significantly affect behavior

decreased exploration in new environment ( J:127250 )

• 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

abnormal spatial learning ( J:127250 )

• 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

increased anxiety-related response ( J:127250 )

• 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

increased thigmotaxis ( J:127250 )

• mice exhibit increased thigmotaxic behavior in an open field and water maze

nervous system

nervous system phenotype ( J:127250 , J:127707 )

N • mice exhibit normal brain morphology, and normal dopaminergic neurons, micro- and astrogliosis in the substantial nigra and locus coeruleus (J:127250)

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)

brain vacuoles ( J:127707 )

• in old-aged mice, neurons display cytoplasmic vacuoles and disruptions in the Golgi network and endoplasmic reticulum

abnormal neuron morphology ( J:127707 )

• 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

abnormal dopamine level ( J:127250 )

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

Genotype
MGI:4939781

hm2

• Allelic Composition: Prkn^tm1Ccs/Prkn^tm1Ccs
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

cellular

abnormal mitochondrial morphology ( J:168847 )

• 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

abnormal CNS glial cell morphology ( J:168847 )

• 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		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease 2		DOID:0060368	OMIM:600116	J:168847

Genotype
MGI:3764819

cx3

• Allelic Composition: Prkn^tm1Ccs/Prkn^tm1Ccs; Tg(CAG-SNCA*)1.1Ccs/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

nervous system

nervous system phenotype ( J:127707 )

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

brain vacuoles ( J:127707 )

• in old-aged mice, neurons display cytoplasmic vacuoles and disruptions in the Golgi network and endoplasmic reticulum

abnormal neuron morphology ( J:127707 )

• 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

abnormal mitochondrial morphology ( J:127707 )

• 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

abnormal cellular respiration ( J:127707 )

• respiration rate is decreased 29.5% when glutamate/malate is used as a substrate after treatment with CCCP

abnormal mitochondrial ATP synthesis coupled electron transport ( J:127707 )

• 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

Genotype
MGI:3764820

cx4

• Allelic Composition: Prkn^tm1Ccs/Prkn^tm1Ccs; Tg(Th-SNCA*)1.2Ccs/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

nervous system

nervous system phenotype ( J:127707 )

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

brain vacuoles ( J:127707 )

• in old-aged mice, neurons display cytoplasmic vacuoles and disruptions in the Golgi network and endoplasmic reticulum

abnormal neuron morphology ( J:127707 )

• 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

abnormal mitochondrial morphology ( J:127707 )

• 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

abnormal cellular respiration ( J:127707 )

• respiration rate is decreased 23.2% when glutamate/malate is used as a substrate after treatment with CCCP

abnormal mitochondrial ATP synthesis coupled electron transport ( J:127707 )

• 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