Phenotypes associated with this allele

• Allele Symbol: Prkn^tm1Roo
• Allele Name: targeted mutation 1, Thomas A Rooney
• Allele ID: MGI:2678247
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Prkn^tm1Roo/Prkn^tm1Roo	either: 129S2/SvPas or (involves: 129S2/SvPas * C57BL/6)	MGI:2678248
hm2	Prkn^tm1Roo/Prkn^tm1Roo	involves: 129S2/SvPas	MGI:3757750
cn3	Gt(ROSA)26Sor^tm1Lrsn/Gt(ROSA)26Sor^+ Prkn^tm1Roo/Prkn^tm1Roo Slc6a3^tm1(cre)Lrsn/Slc6a3^+ Tfam^tm1Lrsn/Tfam^tm1Lrsn	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6	MGI:5292517

Genotype
MGI:2678248

hm1

• Allelic Composition: Prkn^tm1Roo/Prkn^tm1Roo
• Genetic Background: either: 129S2/SvPas or (involves: 129S2/SvPas * C57BL/6)

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

behavior/neurological

decreased exploration in new environment ( J:85561 )

abnormal stationary movement ( J:85561 )

• reduced amphetamine-induced motor activity

growth/size/body

decreased body weight ( J:85561 )

• reduced body weight after weaning, both males and females

homeostasis/metabolism

decreased core body temperature ( J:85561 )

• reduced rectal temperature relative to wild-type

increased dopamine level ( 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

muscle

muscle phenotype ( J:85561 )

N • no evidence of muscle degeneration

nervous system

nervous system phenotype ( J:85561 )

N • brain morphology, weight, and size were normal

abnormal synaptic transmission ( J:85561 )

• 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		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease 2		DOID:0060368	OMIM:600116	J:85561

Genotype
MGI:3757750

hm2

• Allelic Composition: Prkn^tm1Roo/Prkn^tm1Roo
• Genetic Background: involves: 129S2/SvPas

mortality/aging

premature death ( J:125148 )

• null mice have increased mortality risk, displaying early onset of mortality and more rapid decline after 12 months of age

behavior/neurological

abnormal posture ( J:125148 )

abnormal tail movements ( J:125148 )

• mutants display dystonic tails

abnormal locomotor activation ( J:125148 )

• aged mice show dyskinesia and a tendency to reduced mobility

short stride length ( J:125148 )

• significant shortening of hind-limb stride length relative to controls

nervous system

increased neuron apoptosis ( J:125148 )

decreased substantia nigra size ( J:125148 )

• aged mice show reduction in area of substantia nigra

tau protein deposits ( J:125148 )

• 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

loss of dopaminergic neurons ( J:125148 )

• ~35% loss of dopaminergic (tyrosine hydroxylase +ve) neurons in substantia nigra relative to controls or young Park2-null mice

neuron degeneration ( J:125148 )

• cortical neuron degeneration is observed in aged mice

hippocampal neuron degeneration ( J:125148 )

• seen in aged mice

respiratory system

abnormal respiratory function ( J:125148 )

• postural abnormalities cause respiratory problems

skeleton

kyphosis ( J:125148 )

• dorsal kyphosis

integument

alopecia ( J:125148 )

• focal alopecia observed in aged mice

cellular

increased neuron apoptosis ( J:125148 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease 2		DOID:0060368	OMIM:600116	J:125148

Genotype
MGI:5292517

cn3

• Allelic Composition: Gt(ROSA)26Sor^tm1Lrsn/Gt(ROSA)26Sor⁺; Prkn^tm1Roo/Prkn^tm1Roo; Slc6a3^tm1(cre)Lrsn/Slc6a3⁺; Tfam^tm1Lrsn/Tfam^tm1Lrsn
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6

nervous system

abnormal neuron morphology ( J:176022 )

• 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

loss of dopaminergic neurons ( J:176022 )

abnormal axonal transport ( J:176022 )

• neurons exhibit less intense staining with a retrograde tracer (fluorogold) suggesting impaired retrograde transport and/or uptake of the tracer compared with control cells