Research Models

PINK1 G309D (PINK1-/-) Mouse (KI)

Synonyms: Pink1-, Pink1-deficient mouse, PARK6 mouse, Pink1-/-, PINK1 G309D (PINK1-) KI Mouse (Auburger)

Species: Mouse
Genes: PINK1
Mutations: Pink1 G309D
Modification: PINK1: Knock-In
Disease Relevance: Parkinson's Disease
Strain Name: B6;129-Pink1tm1Aub/J
Genetic Background: The vector was introduced into a 129/SvEV-derived embryonic stem cell line. Resulting chimeric mice were bred and maintained on a pure 129 background.
Availability: Available through The Jackson Laboratory, Stock# 013050, Cryopreserved.


This mouse model is referred to as Pink1-/-. It is not a genetic knockout, but carries an incorrectly spliced and unstable Pink1 mRNA resulting in deficiency of PINK1 protein. This model was initially designed to carry a knock-in mutation (PINK1 G309D) and it can be converted to this knock-in status by crossing it with Cre/loxP-deleter mice.The G309D mutation introduced at the orthologous murine locus, is a loss-of-function mutation responsible for a recessive form of Parkinson’s disease, associated with PINK1 deficiency (Valente et al., 2004; Bentivoglio et al., 2001).

Pink1 expression was essentially abolished in homozygous Pink1-/- mice (Gispert et al., 2009). Levels of Pink1 RNA were reduced 97 percent in the brains of homozygous mice. It was not possible to assess whether there was a corresponding reduction in PINK1 protein.

Body weight of homozygous Pink1-/- mice is lower than non-transgenic mice by 10 months of age. It is unclear if this is primarily due to differences in food intake, metabolism, or behavior. Homozygous mice exhibited reduced spontaneous locomotor activity by 16 months of age as measured by total distance traveled in the open-field test. The 129/SvEv strain in general is known to have a relatively low baseline activity level. Measures of strength, coordination, and anxiety were normal (Gispert et al., 2009).

Other nervous system functions appear intact. The mice behaved similarly to non-transgenic mice in tests assessing their startle reflex and sweating. Lifespan was normal (Gispert et al., 2009).

The brains of these mice were grossly normal. There were no obvious structural differences in the brainstem, cerebellum, or cerebrum. Likewise, there was no measurable neuronal loss at 18 months of age, either in the general neuronal population or specifically in dopaminergic neurons. However, by nine months of age, Pink1-/- mice had lower concentrations of striatal dopamine. This was also observed at 22-24 months (Gispert et al., 2009).

Differences in electrophysiological activity have been detected from a young age. Recordings from postnatal midbrain dopaminergic neurons revealed abnormal glutamatergic activity (Pearlstein et al., 2016). Recordings from juvenile motor cortex demonstrated hypersynchrony (Carron et al., 2014). In young adult mice, recordings from the basal ganglia revealed an electrophysiological signature consistent with dopamine depletion, including giant GABAergic currents in striatal medium spiny neurons and a shift in the spontaneous activity of subthalamic nucleus neurons from single spikes to rhythmic bursts (Dehorter et al., 2012 ).

Pink1-/- mice appear to have little evidence of typical PD-related neuropathology. They do not develop detectable Lewy bodies or α-synuclein aggregates in the brainstem or substantia nigra. They do have slightly more α-synuclein immunoreactivity in the dorsal motor nucleus of the vagus (Gispert et al., 2009).

Depletion of PINK1 affects cannabinoid receptor expression in an age-dependent manner. By nine months of age, cannabinoid receptor-1 levels are reduced in the nigrostriatal tract, however they are elevated above control levels at advanced age (e.g., 24 months) (García-Arencibia et al., 2009).

PINK1 is a mitochondrial protein kinase, and perhaps the most striking phenotype in this model is age-associated mitochondrial dysfunction. The mitochondria of PINK1-deficient mice appear normal in terms of morphology and mass, but they display a fission deficit. Cultured neurons showed reduced respiratory activity, reduced ATP production, and a decrease in membrane potential (Gispert et al., 2009).

Transcriptomic analyses of cerebellar, midbrain, and striatal tissues, as well as neuron-rich primary cultures, revealed subtle alterations in gene expression at 1.5, six, and 18 months (Torres-Odio et al., 2017). The authors highlight early cerebellar changes in the expression of factors involved in splicing, subsequent alterations in ubiquitin-mediated proteolysis and endoplasmic reticulum processing, and a late increase in toll-like receptor signaling involved in innate immunity. Moderate increases in astrocytic and microglial markers were detected at 18 months in the striatum and along the corticospinal tract where it traverses the brainstem.

Modification Details

A targeting vector was used to introduce a 4.2 kb fragment of the Pink1 gene into the orthologous mouse locus. The vector contained exons 2, 3, 4, and 5 as well as an additional 3. 2 kb. The G309D mutation was introduced in exon 4 by site-directed mutagenesis.

Related Strains

PINK1 ablation x A53T-SNCA- This is a double mutant (Gispert et al., 2015) made by crossing Pink1-/- mice (inbred 129Sv/Ev background) with transgenics expressing mutant α-synuclein (A53T) driven by the prion protein promoter (inbred FVB/N background) (Gispert et al., 2003). This digenic model of PD shows potentiated neurotoxicity with a shortened lifespan  (see also Auburger et al., 2014; Auburger et al., 2016). Available through The Jackson Laboratory, Stock# 017678, Cryopreserved.

Phenotype Characterization

When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.


  • Non-Motor Impairment
  • α-synuclein Inclusions
  • Neuronal Loss

No Data

Neuronal Loss

Neuronal loss was not observed at 18 months of age (total neuronal population and TH-positive subset).

Dopamine Deficiency

Decreased dopamine concentration in the striatum by 9 months of age.

α-synuclein Inclusions

No Lewy body-like inclusions of α-synuclein aggregates in the brainstem or substantia nigra, but the expression levels of alpha-synuclein are altered in brainstem/midbrain.


Expression of factors involved in toll-like receptor signaling increased in the cerebellum, as did astrocytic and microglial markers in the corticospinal tract and striatum at 18 months.

Mitochondrial Abnormalities

By 3 months of age the mice exhibited a mitochondrial import defect. This phenotype was more severe at 6 months and import was reduced nearly 50% by 12 months of age. By 6 months, ATP production, respiration, and mitochondrial membrane potential were also reduced.

Motor Impairment

At 16 months of age Pink1-/- mice exhibited decreased spontaneous locomotor activity. Strength and coordination were intact.

Non-Motor Impairment

Mutant mice performed similarly to wild-type mice in tests assessing the startle reflex, sweating, and anxiety.

Last Updated: 11 Feb 2019


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Paper Citations

  1. . Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science. 2004 May 21;304(5674):1158-60. Epub 2004 Apr 15 PubMed.
  2. . Phenotypic characterisation of autosomal recessive PARK6-linked parkinsonism in three unrelated Italian families. Mov Disord. 2001 Nov;16(6):999-1006. PubMed.
  3. . Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration. PLoS One. 2009;4(6):e5777. PubMed.
  4. . Abnormal Development of Glutamatergic Synapses Afferent to Dopaminergic Neurons of the Pink1(-/-) Mouse Model of Parkinson's Disease. Front Cell Neurosci. 2016;10:168. Epub 2016 Jun 23 PubMed.
  5. . Early hypersynchrony in juvenile PINK1(-)/(-) motor cortex is rescued by antidromic stimulation. Front Syst Neurosci. 2014;8:95. Epub 2014 May 21 PubMed.
  6. . Subthalamic lesion or levodopa treatment rescues giant GABAergic currents of PINK1-deficient striatum. J Neurosci. 2012 Dec 12;32(50):18047-53. PubMed.
  7. . Cannabinoid CB1 receptors are early downregulated followed by a further upregulation in the basal ganglia of mice with deletion of specific park genes. J Neural Transm Suppl. 2009;(73):269-75. PubMed.
  8. . Progression of pathology in PINK1-deficient mouse brain from splicing via ubiquitination, ER stress, and mitophagy changes to neuroinflammation. J Neuroinflammation. 2017 Aug 2;14(1):154. PubMed.
  9. . Potentiation of neurotoxicity in double-mutant mice with Pink1 ablation and A53T-SNCA overexpression. Hum Mol Genet. 2015 Feb 15;24(4):1061-76. Epub 2014 Oct 8 PubMed.
  10. . Transgenic mice expressing mutant A53T human alpha-synuclein show neuronal dysfunction in the absence of aggregate formation. Mol Cell Neurosci. 2003 Oct;24(2):419-29. PubMed.
  11. . Mitochondrial acetylation and genetic models of Parkinson's disease. Prog Mol Biol Transl Sci. 2014;127:155-82. PubMed.
  12. . Methyl-Arginine Profile of Brain from Aged PINK1-KO+A53T-SNCA Mice Suggests Altered Mitochondrial Biogenesis. Parkinsons Dis. 2016;2016:4686185. Epub 2016 Mar 1 PubMed.

External Citations

  1. The Jackson Laboratory, Stock# 017678
  2. The Jackson Laboratory, Stock# 013050

Further Reading

No Available Further Reading