Phenotypes associated with this allele

• Allele Symbol: Pink1^tm1Aub
• Allele Name: targeted mutation 1, Georg Auburger
• Allele ID: MGI:3850370
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Pink1^tm1Aub/Pink1^tm1Aub	involves: 129S/SvEv	MGI:3850371
cx2	Pink1^tm1Aub/Pink1^tm1Aub Tg(Prnp-SNCA*A53T)AAub/Tg(Prnp-SNCA*A53T)AAub	involves: 129S/SvEv * FVB/N	MGI:5604250

Genotype
MGI:3850371

hm1

• Allelic Composition: Pink1^tm1Aub/Pink1^tm1Aub
• Genetic Background: involves: 129S/SvEv

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

nervous system

nervous system phenotype ( J:150206 )

N • despite decreased dopamine levels, no loss of dopaminergic neurons is seen at 18 months of age

N • unlike in Parkinson's disease patients, Lewy bodies are not detected in the brainstem and substantia nigra

behavior/neurological

behavior/neurological phenotype ( J:150206 )

N • unlike in human patients with early stage sporadic Parkinson's disease, acoustic startle reflexes are not impaired

decreased locomotor activity ( J:150206 )

• decrease in total distance covered, horizontal activity, movement time, stereotypy count and center distance in an open field test beginning at 16 months of age

growth/size/body

decreased body weight ( J:150206 )

• weigh up to 19% less than controls at 1 year of age

cellular

cellular phenotype ( J:150206 )

N • unlike in Drosophila pink1 null mutants, no defects in mitochondrial fission are detected

abnormal cellular respiration ( J:150206 )

• decrease in ATP levels in dissociated neurons under basal conditions

• liver mitochondrial membrane potential shows a progressive age related reduction

abnormal mitochondrial physiology ( J:150206 )

• assays indicate age-related impairment in liver mitochondrial import reactions

abnormal respiratory electron transport chain ( J:150206 )

• liver mitochondrial membrane potential shows a progressive age related reduction

abnormal mitochondrial ATP synthesis coupled electron transport ( J:150206 )

• respiratory complex activity of purified liver mitochondria from 18 month old mice is significantly reduced compared to controls

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:150206 )

N • unlike in human patients with early stage sporadic Parkinson's disease, increased sweating is not seen

homeostasis/metabolism

decreased dopamine level ( J:150206 )

• decreased dopamine levels in the striatum at 9 and 22-24 months of age

mortality/aging

extended life span ( J:214065 )

• mortality rate is reduced as compared to wild-type controls

• most mice live to 450 days, some live to greater than 600 days

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease 6		DOID:0060369	OMIM:605909	J:150206

Genotype
MGI:5604250

cx2

• Allelic Composition: Pink1^tm1Aub/Pink1^tm1Aub; Tg(Prnp-SNCA*A53T)AAub/Tg(Prnp-SNCA*A53T)AAub
• Genetic Background: involves: 129S/SvEv * FVB/N

behavior/neurological

abnormal locomotor behavior ( J:214065 )

decreased vertical activity ( J:214065 )

• reduction in vertical activity by 3 months of age

decreased locomotor activity ( J:214065 )

• reductions in horizontal activity by 3 months of age

hindlimb paralysis ( J:214065 )

• 25% of mice exhibit progressive hindlimb paralysis at ages greater than 1 year

paresis ( J:214065 )

• 16/60 mice older than one year exhibit flaccid paresis of the hindlimbs, progressing to full paraplegia

decreased stereotypic behavior ( J:214065 )

• reductions in stereotype movement counts by 3 months of age

mortality/aging

premature death ( J:214065 )

• late onset increase in mortality rate at 450 days as compared to wild-type controls

• some mice develop a lethal motor deficit at greater than one year

nervous system

abnormal motor neuron morphology ( J:214065 )

• protein aggregates with pSer129-SNCA, P62, and ubiquitin immunoreactivity appears as granular and thread-like in neuronal cytoplasm of neurons with extensions along neurites

abnormal neurite morphology ( J:214065 )

• some neurites exhibit corkscrew morphology

alpha-synuclein inclusion body ( J:214065 )

• protein aggregates with pSer129-SNCA, P62 and ubiquitin immunoreactivity are observed in grey matter of lumbar spinal cord of paralyzed animals aged to 15-17 months

• aggregate pathology is milder in thoracic and cervical spinal cord

• immunoreactivity appears as granular and thread-like in neuronal cytoplasm of neurons with extensions along neurites

• protein aggregates are observed in non-paralyzed animals, but with little neurite pathology

• discrete lesions are found in motor cortex, but not striatum of paralyzed mice

• minimal lesions are found in ventral tegmental area of non-paralytic mice

• aggregate formation is found in non-dopaminergic neurons (NeuN-positive)

• no aggregate formation is found in dopaminergic neurons

neurodegeneration ( J:214065 )

skeleton

kyphosis ( J:214065 )

• 3/60 mice older than one year exhibit kyphosis, falls and rigidity

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease		DOID:14330	OMIM:PS168600	J:214065