Strain Name:

B6.129S4-Pink1tm1Shn/J

Stock Number:

017946

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Availability:

Repository- Live

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These Pink1 knockout mice exhibit reduced mean evoked dopamine overflow, altered dopamine signaling, and have applications in studies related to Parkinson's disease.

Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Mating SystemHeterozygote x Heterozygote         (Female x Male)   10-JUL-13
Specieslaboratory mouse
GenerationN7+pN1 (24-SEP-13)
Generation Definitions
 
Donating Investigator Jie Shen,   Harvard Med Sch/Brigham Women's Hosp

Description
These Pink1 (PTEN induced putative kinase 1) knockout mice have exons 4 through 7 deleted, disrupting most of the kinase domain and producing a nonsense mutation at the start of exon 8 due to a reading frame shift. Missense mutations in the PINK1 gene cause autosomal-recessive Parkinson's disease. PINK1 loss of function results in mitochondrial dysfunction, increased reactive oxygen species production and calcium homeostasis imbalance. Homozygous mutant mice are viable and fertile. No Pink1 mRNA is detected by Northern blot analysis in brain tissue from homozygotes. Evoked release of striatal dopamine and catecholamine, and catecholamine release by adrenal chromaffin cells is decreased in homozygotes. Dopamine levels in the striatum, dopaminergic neuron number, dopamine synthesis and dopamine receptor number are not altered. Homozygotes exhibit impaired induction of long-term potentiation and long-term depression at corticostriatal synapses. No nigrostriatal neurodegeneration is detected in homozygous mice 9 months of age. Homozygotes are more sensitive to metabotropic glutamate (mGlu) receptor agonist than wildtype controls.

Development
A targeting vector containing a PGK-NEO cassette was used to disrupt exons 4 through 7. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to generate homozygotes. The mice were then backcrossed to C57BL/6J for 7 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

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008333   B6;129P2-Dldtm1Ptl/J
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003243   B6;129S-Tnfrsf1atm1Imx Tnfrsf1btm1Imx/J
003692   B6;129X1-Sncatm1Rosl/J
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View Parkinson's Disease Models     (112 strains)

Strains carrying other alleles of Pink1
013050   B6;129-Pink1tm1Aub/J
017678   FVB;129-Pink1tm1Aub Tg(Prnp-SNCA*A53T)AAub/J
View Strains carrying other alleles of Pink1     (2 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
Parkinson Disease 6, Autosomal Recessive Early-Onset; PARK6
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Pink1tm1Shn/Pink1tm1Shn

        involves: 129S4/SvJae * C57BL/6
  • nervous system phenotype
  • abnormal nervous system physiology
    • catecholamine release is lower than in wild-type mice   (MGI Ref ID J:122728)
    • decreased dopamine level
      • the mean evoked dopamine overflow is significantly decreased in striatal slices from 2 to 3 month old mice compared to wild-type   (MGI Ref ID J:122728)
      • release of dopamine is decreased   (MGI Ref ID J:122728)
      • however, the number of D1 and D2 receptors is normal   (MGI Ref ID J:122728)
    • reduced long term depression
      • long term depression (LTD) is impaired   (MGI Ref ID J:122728)
      • however, LTD can be rescued using D1 and D2 agonists and amphetamine   (MGI Ref ID J:122728)
    • reduced long term potentiation
      • long term potential (LTP) induced by high frequency stimulation in the absence of magnesium is lower than in wild-type mice   (MGI Ref ID J:122728)
      • however, LTP can be rescued using D1 receptor-like agonists   (MGI Ref ID J:122728)
  • homeostasis/metabolism phenotype
  • decreased dopamine level
    • the mean evoked dopamine overflow is significantly decreased in striatal slices from 2 to 3 month old mice compared to wild-type   (MGI Ref ID J:122728)
    • release of dopamine is decreased   (MGI Ref ID J:122728)
    • however, the number of D1 and D2 receptors is normal   (MGI Ref ID J:122728)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Neurobiology Research
Parkinson's Disease

Research Tools
Neurobiology Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Pink1tm1Shn
Allele Name targeted mutation 1, Jie Shen
Allele Type Targeted (Null/Knockout)
Common Name(s) Pink1-;
Strain of Origin129S4/SvJae
Gene Symbol and Name Pink1, PTEN induced putative kinase 1
Chromosome 4
Gene Common Name(s) 1190006F07Rik; AU042772; AW557854; BRPK; PARK6; RIKEN cDNA 1190006F07 gene; expressed sequence AU042772; expressed sequence AW557854;
Molecular Note Exons 4-7 were replaced with a pgk-neo cassette via cre mediated recombination, thereby removing the majority of the kinase domain and creating a nonsense mutation at the beginning of exon 8. Northern blot confirmed absence of transcript in mutants. [MGI Ref ID J:122728]

Genotyping

Genotyping Information

Genotyping Protocols

Pink1tm1Shnalternate1, High Resolution Melting


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Kitada T; Pisani A; Porter DR; Yamaguchi H; Tscherter A; Martella G; Bonsi P; Zhang C; Pothos EN; Shen J. 2007. From the Cover: Impaired dopamine release and synaptic plasticity in the striatum of PINK1-deficient mice. Proc Natl Acad Sci U S A 104(27):11441-6. [PubMed: 17563363]  [MGI Ref ID J:122728]

Additional References

Pink1tm1Shn related

Gautier CA; Kitada T; Shen J. 2008. Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stress. Proc Natl Acad Sci U S A 105(32):11364-9. [PubMed: 18687901]  [MGI Ref ID J:140335]

Haque ME; Mount MP; Safarpour F; Abdel-Messih E; Callaghan S; Mazerolle C; Kitada T; Slack RS; Wallace V; Shen J; Anisman H; Park DS. 2012. Inactivation of Pink1 Gene in Vivo Sensitizes Dopamine-producing Neurons to 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and Can Be Rescued by Autosomal Recessive Parkinson Disease Genes, Parkin or DJ-1. J Biol Chem 287(27):23162-70. [PubMed: 22511790]  [MGI Ref ID J:186202]

Kueh SL; Dempster J; Head SI; Morley JW. 2011. Reduced postsynaptic GABA(A) receptor number and enhanced gaboxadol induced change in holding currents in Purkinje cells of the dystrophin-deficient mdx mouse. Neurobiol Dis :. [PubMed: 21601636]  [MGI Ref ID J:173345]

Madeo G; Martella G; Schirinzi T; Ponterio G; Shen J; Bonsi P; Pisani A. 2012. Aberrant striatal synaptic plasticity in monogenic parkinsonisms. Neuroscience 211:126-35. [PubMed: 21839811]  [MGI Ref ID J:184659]

Mannam P; Shinn AS; Srivastava A; Neamu RF; Walker WE; Bohanon M; Merkel J; Kang MJ; Dela Cruz CS; Ahasic AM; Pisani MA; Trentalange M; West AP; Shadel GS; Elias JA; Lee PJ. 2014. MKK3 regulates mitochondrial biogenesis and mitophagy in sepsis-induced lung injury. Am J Physiol Lung Cell Mol Physiol 306(7):L604-19. [PubMed: 24487387]  [MGI Ref ID J:210185]

Martella G; Madeo G; Schirinzi T; Tassone A; Sciamanna G; Spadoni F; Stefani A; Shen J; Pisani A; Bonsi P. 2011. Altered profile and D2-dopamine receptor modulation of high voltage-activated calcium current in striatal medium spiny neurons from animal models of Parkinson's disease. Neuroscience 177:240-51. [PubMed: 21195752]  [MGI Ref ID J:170553]

Martella G; Platania P; Vita D; Sciamanna G; Cuomo D; Tassone A; Tscherter A; Kitada T; Bonsi P; Shen J; Pisani A. 2009. Enhanced sensitivity to group II mGlu receptor activation at corticostriatal synapses in mice lacking the familial parkinsonism-linked genes PINK1 or Parkin. Exp Neurol 215(2):388-96. [PubMed: 19071114]  [MGI Ref ID J:144364]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice can be bred as homozygotes.
Mating SystemHeterozygote x Heterozygote         (Female x Male)   10-JUL-13

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $199.90Female or MaleHomozygous for Pink1tm1Shn  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $259.90Female or MaleHomozygous for Pink1tm1Shn  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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