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| These Parkin-Q311X(A) mice express a 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. These Parkin-Q311X(A) mice represent a robust in vivo model for studying the multiple late-onset and progressive Parkinson's disease pathogenesis (hypokinetic motor deficits, dopaminergic neuron dysfunction and degeneration, and age-dependent accumulation of proteinase K-resistant endogenous alpha-synuclein) elicited by the dominant toxic effects of mutant parkin-Q311X expression. | |||||||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
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 System Hemizygote x Noncarrier (Female x Male) 09-FEB-10 Species laboratory mouse Generation F?+F3 (14-MAR-11)
Generation DefinitionsDonating 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 | ||
Related Strains
Parkinson's Disease Models
View Parkinson's Disease Models (109 strains)
006660 B6.SJL-Slc6a3tm1.1(cre)Bkmn/J 016583 C57BL/6N-Tg(Slc6a3-icre/ERT2)2Gloss/J
Additional Web Information
Visit the Parkinson's Disease Resource site for helpful information on Parkinson's and research resources.
Phenotype
Phenotype Information
- 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)
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)
- 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)
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 (random, expressed) | ||
| Common Name(s) | Parkin-Q311X line A; Parkin-Q311X(A); TgA; | ||
| Mutation Made By | X. William Yang, University of California Los Angeles | ||
| Strain of Origin | FVB/NJ | ||
| Expressed Gene | PARK2, parkinson protein 2, E3 ubiquitin protein ligase (parkin), 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 AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, hemizygous mice may be bred to wildtype (noncarrier) siblings or to FVB/NJ inbred mice (Stock No. 001800). Mating System Hemizygote 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 |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $232.00 Female or Male Hemizygous for Tg(Slc6a3-PARK2*Q311X)AXwy
Price per Pair (US dollars $) Pair Genotype $296.00 Hemizygous for Tg(Slc6a3-PARK2*Q311X)AXwy x Noncarrier $296.00 Noncarrier x Hemizygous for Tg(Slc6a3-PARK2*Q311X)AXwy Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
| Pricing for International shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $301.60 Female or Male Hemizygous for Tg(Slc6a3-PARK2*Q311X)AXwy
Price per Pair (US dollars $) Pair Genotype $384.80 Hemizygous for Tg(Slc6a3-PARK2*Q311X)AXwy x Noncarrier $384.80 Noncarrier x Hemizygous for Tg(Slc6a3-PARK2*Q311X)AXwy Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
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Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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