Strain Name:

FVB/NJ-Tg(Slc6a3-PARK2*Q311X)AXwy/J

Stock Number:

009090

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Availability:

Repository- Live

Use Restrictions Apply, see Terms of Use
This transgenic strain carries a modified Slc6a3-parkin-Q311X (a FLAG-tagged mutant human parkin gene) BAC. These mice are useful for studying Parkinson's disease pathogenesis and neurodegeneration.

Description

Strain Information

Former Names FVB/N-Tg(Slc6a3-PARK2*Q311X)AXwy/J    (Changed: 08-JUL-09 )
Type Coisogenic; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Mating SystemHemizygote x Noncarrier         (Female x Male)   09-FEB-10
Specieslaboratory mouse
GenerationF?+F7 (12-DEC-13)
Generation Definitions
 
Donating Investigator X. William Yang,   University of California Los Angeles

Description
Hemizygous Parkin-Q311X(A) mice are viable and fertile, with expression of a FLAG-tagged, C-terminal truncated human parkin-Q311X mutation associated with Turkish early-onset Parkinson's disease directed to dopaminergic neurons of the substantia nigra pars compacta (SNc) and ventral tegmentum area (VTA) by the mouse Slc6a3 promoter/enhancer sequences. Parkin-Q311X(A) mice (derived from founder line A) have expression of the FLAG-tagged parkin-Q311X protein in dopaminergic neurons at a level that is approximately equivalent to or just below that expected from a heterozygous endogenous parkin allele. Parkin-Q311X(A) mice exhibit multiple late-onset and progressive hypokinetic motor deficits, progressive dopaminergic neuron dysfunction and degeneration, and age-dependent accumulation of proteinase K-resistant endogenous alpha-synuclein. Compared to founder line D, Parkin-Q311X(A) mice have a higher transgene copy number that results in more robust and earlier onset of hypokinetic motor deficits and more significant dopaminergic (DA) neuron degeneration. These Parkin-Q311X(A) mice represent a robust in vivo model for studying the Parkinson's disease pathogenesis and neurodegeneration elicited by the dominant toxic effects of mutant parkin-Q311X expression.

View PD Online Research Q&A with Dr. X. William Yang: The Parkin-Q311X model.

Development
The 200 kb mouse bacterial artificial chromosome (BAC) RP23-408F13 contains the entire 50 kb Slc6a3 gene (solute carrier family 6 (neurotransmitter transporter, dopamine), member 3; also called dopamine transporter (DAT)) and other genes in the approximately 100 kb of 5' and 40 kbp of 3' flanking sequences. This BAC was modified by inserting a parkin-Q311X cDNA sequence (FLAG-tagged mutant human parkin gene (PARK2; Parkinson disease (autosomal recessive, juvenile) 2, parkin) carrying the Q311X truncation associated with Turkish early-onset Parkinson's disease and followed by a polyA signal) into Slc6a3 exon 2 upstream of the translation initiation codon. This modified Slc6a3-parkin(Q311X) BAC was microinjected into fertilized FVB/NJ zygotes. Parkin-Q311X mice from founder line A (found to harbor two tandem integrates of the transgene) were subsequently maintained by breeding transgenic mice with wildtype (noncarrier) siblings or FVB/NJ inbred mice for many generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred to FVB/NJ inbred mice (Stock No. 001800) for at least one generation to establish the colony.

Control Information

  Control
   Noncarrier
   001800 FVB/NJ
 
  Considerations for Choosing Controls

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View Strains carrying other alleles of Slc6a3     (4 strains)

Additional Web Information

Visit the Parkinson's Disease Resource site for helpful information on Parkinson's and research resources.

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.
Parkinson Disease 2, Autosomal Recessive Juvenile; PARK2
- Potential model based on transgenic expression of an ortholog of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested.
Leprosy, Susceptibility to, 2; LPRS2   (PARK2)
Lung Cancer   (PARK2)
Ovarian Cancer   (PARK2)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Tg(Slc6a3-PARK2*Q311X)AXwy/0

        FVB/NJ-Tg(Slc6a3-PARK2*Q311X)AXwy
  • behavior/neurological phenotype
  • abnormal locomotor activation
    • at 16-19 months, mice make significantly fewer hindlimb steps compared to controls   (MGI Ref ID J:146833)
    • decreased vertical activity
      • in cylinder tests, mice show decreased rearing compared to controls at 16-19 months   (MGI Ref ID J:146833)
    • hypoactivity
      • at 3, 12, 16, and 21 months of age, mice display significantly progressive hypoactivity in open field tests   (MGI Ref ID J:146833)
  • abnormal touch/ nociception
    • in adhesive removal tests, at 16-19 months, mutants show significant deficits at 16-19 months   (MGI Ref ID J:146833)
  • impaired balance
    • in beam tests, mice show more errors per step while traversing the beam compared with age; significant age effect is observed with performance in 3-6 month-old animals being comparable to controls but markedly impaired at 16-19 months   (MGI Ref ID J:146833)
  • nervous system phenotype
  • abnormal substantia nigra morphology
    • in the middle and caudal regions of the substantia nigra, significant numbers of alpha synuclein positive neurons are detected at 16 months, but not at 3 months; a chronic accumulation of proteinase K-resistant alpha-synuclein in midbrain neurons is observed in mutants   (MGI Ref ID J:146833)
    • dopaminergic neurons in the substantia nigra display oxidative protein damage at 16 months which is not as prevalent in wild-type mice   (MGI Ref ID J:146833)
  • decreased dopamine level
    • in 19-21 month-old animals, dopamine (DA) levels are significantly reduced compared to controls which correlates with multiple hypokinetic motor deficits like open-field motor activity and vertical plane entries   (MGI Ref ID J:146833)
  • loss of dopaminergic neurons
    • at 16 months, mice have a 40% reduction in tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta (SNc) coincident with a 30% reduction in total neuron number indicating a late-onset dopaminergic neuron loss   (MGI Ref ID J:146833)
  • integument phenotype
  • abnormal touch/ nociception
    • in adhesive removal tests, at 16-19 months, mutants show significant deficits at 16-19 months   (MGI Ref ID J:146833)
  • homeostasis/metabolism phenotype
  • decreased dopamine level
    • in 19-21 month-old animals, dopamine (DA) levels are significantly reduced compared to controls which correlates with multiple hypokinetic motor deficits like open-field motor activity and vertical plane entries   (MGI Ref ID J:146833)
View Research Applications

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

Developmental Biology Research
Neurodevelopmental Defects

Neurobiology Research
Ataxia (Movement) Defects
Cortical Defects
Neurodegeneration
Neurodevelopmental Defects
Parkinson's Disease
      Park2 (parkin) mutants
Tremor Defects

Research Tools
Neurobiology Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tg(Slc6a3-PARK2*Q311X)AXwy
Allele Name transgene insertion A, X William Yang
Allele Type Transgenic (Inserted expressed sequence)
Common Name(s) Parkin-Q311X line A; Parkin-Q311X(A); TgA;
Mutation Made By X. William Yang,   University of California Los Angeles
Strain of OriginFVB/NJ
Expressed Gene PARK2, parkin RBR E3 ubiquitin protein ligase, human
Promoter Slc6a3, solute carrier family 6 (neurotransmitter transporter, dopamine), member 3, mouse, laboratory
Molecular Note A 200 kb mouse bacterial artificial chromosome (BAC) RP23-408F13 contains the entire 50 kb Slc6a3 gene (solute carrier family 6 (neurotransmitter transporter, dopamine), member 3; also called dopamine transporter (DAT)) and other genes in the approximately 100 kb of 5' and 40 kbp of 3' flanking sequences. This BAC was modified by inserting a parkin-Q311X cDNA sequence (FLAG-tagged mutant human parkin gene (PARK2; Parkinson disease (autosomal recessive, juvenile) 2, parkin) carrying the Q311X truncation associated with Turkish early-onset Parkinson's disease and followed by a polyA signal) into Slc6a3 exon 2 upstream of the translation initiation codon. This modified Slc6a3-parkin(Q311X) BAC was microinjected into fertilized FVB/NJ zygotes. Line A (found to harbor two tandem integrates of the transgene) was subsequently established. [MGI Ref ID J:146833]
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(Slc6a3-PARK2*Q311X), Melt Curve Analysis
Tg(Slc6a3-PARK2*Q311X), Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Lu XH; Fleming SM; Meurers B; Ackerson LC; Mortazavi F; Lo V; Hernandez D; Sulzer D; Jackson GR; Maidment NT; Chesselet MF; Yang XW. 2009. Bacterial artificial chromosome transgenic mice expressing a truncated mutant parkin exhibit age-dependent hypokinetic motor deficits, dopaminergic neuron degeneration, and accumulation of proteinase K-resistant alpha-synuclein. J Neurosci 29(7):1962-76. [PubMed: 19228951]  [MGI Ref ID J:146833]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX10

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, hemizygous mice may be bred to wildtype (noncarrier) siblings or to FVB/NJ inbred mice (Stock No. 001800).
Mating SystemHemizygote x Noncarrier         (Female x Male)   09-FEB-10
Diet Information LabDiet® 5K52/5K67

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 $239.00Female or MaleHemizygous for Tg(Slc6a3-PARK2*Q311X)AXwy  
Price per Pair (US dollars $)Pair Genotype
$311.00Hemizygous for Tg(Slc6a3-PARK2*Q311X)AXwy x Noncarrier  
$311.00Noncarrier x Hemizygous for Tg(Slc6a3-PARK2*Q311X)AXwy  

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 $310.70Female or MaleHemizygous for Tg(Slc6a3-PARK2*Q311X)AXwy  
Price per Pair (US dollars $)Pair Genotype
$404.30Hemizygous for Tg(Slc6a3-PARK2*Q311X)AXwy x Noncarrier  
$404.30Noncarrier x Hemizygous for Tg(Slc6a3-PARK2*Q311X)AXwy  

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
   Noncarrier
   001800 FVB/NJ
 
  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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