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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
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 System Homozygote x Homozygote (Female x Male) 01-JUL-08 Species laboratory mouse Generation N22+F5 (01-DEC-09)
Generation DefinitionsDonating Investigator Jie Shen, Harvard Med Sch/Brigham Women's Hosp Description
Homozygous mice are viable and fertile, and exhibit grossly normal brain morphology. Western blot analysis using antibody specific to C-terminal sequences indicates the absence of full length gene product. RT-PCR shows that exon 2 splices to exon 4, skipping exon 3 entirely, resulting in a frame shift and a premature stop codon in exon 5. While EGFP transcripts are present, little parkin-EGFP fusion protein is detectable by Western analysis. Homozygous mice have increased extracellular dopamine concentration in the striatum. Further, medium-sized striatal spiny neurons require greater currents to induce synaptic responses, suggesting a reduction in synaptic excitability in the absence of the endogenous gene. Homozygotes also exhibit deficits in behavioral paradigms sensitive to dysfunction of the nigrostriatal pathway. The numbers of dopaminergic neurons in the substantia nigra, however, are normal up to the age of 24 months, in contrast to the substantial loss of nigral neurons characteristic of Parkinson's disease. Homozygous mice and their isolated cells exhibit mitochondrial dysfunction and impaired protection from oxidative stress. Muscle cells isolated from homozygous mice have defective skeletal muscle mitochondrial homeostasis and increased sensitivity to amyloid-beta toxicity. These mice model the exon 3 deleti on mutation most common in human autosomal recessive juvenile parkinsonism (AR-JP) patients and may be useful in studies of Parkinson's disease, dopamine regulation, nigrostriatal function, mitochondrial function, and other neurobiological research.In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. Mice with this mutation were originally published on a mixed B6;129S4 genetic background. It should be noted that the phenotype could vary from that originally described. The strain description will be modified as published results become available.
Development
A targeting vector was designed to replace most of exon 3 of the endogenous gene with the in-frame EGFP coding sequence (followed by translation and transcription termination sequences and a PGK-neomycin cassette). The construct was electroporated into the 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting mutant mice were backcrossed to C57BL/6 inbred mice for more than 20 generations before arriving at The Jackson Laboratory.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Parkinson's Disease Models
View Parkinson's Disease Models (99 strains)
007587 129S-Park2tm1Rpa/J
Additional Web Information
Visit the Parkinson's Disease Resource site for helpful information on Parkinson's and research resources.
Phenotype
Phenotype Information
Parkinson Disease 2, Autosomal Recessive Juvenile; PARK2 - Models with phenotypic similarity to human disease where etiologies involve orthologs.1
1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s). assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Park2tm1Shn/Park2tm1Shn
involves: 129S4/SvJae
- behavior/neurological phenotype
- impaired coordination
- nervous system phenotype
- abnormal nervous system electrophysiology
- higher currents are required in striatal neurons to trigger synaptic response (MGI Ref ID J:86377)
- increased dopamine level
- higher than normal levels of dopamine in the striatum (MGI Ref ID J:86377)
- homeostasis/metabolism phenotype
- increased dopamine level
- higher than normal levels of dopamine in the striatum (MGI Ref ID J:86377)
This mouse can be used to support research in many areas including:
Neurobiology Research
Parkinson's Disease
Park2 (parkin) mutants
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Park2tm1Shn | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Jie Shen | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | parkin -; | ||
| Mutation Made By | Jie Shen, Harvard Med Sch/Brigham Women's Hosp | ||
| Strain of Origin | 129S4/SvJae | ||
| ES Cell Line Name | J1 | ||
| ES Cell Line Strain | 129S4/SvJae | ||
| Gene Symbol and Name | Park2, Parkinson disease (autosomal recessive, juvenile) 2, parkin | ||
| Chromosome | 17 | ||
| Gene Common Name(s) | AR-JP; LPRS2; PDJ; PRKN; Park; | ||
| Molecular Note | Exon 3 was replaced in-frame by the coding sequence for EGFP followed by a PGK-neomycin cassette. RT-PCR analysis indicated that exon 2 spliced to exon 4 in transcripts thus skipping exon 3 entirely. This results in a frame shift and a premature stop codon in exon 5. Western blot analysis using antibody specific to C-terminal sequences indicated the absence of gene product. [MGI Ref ID J:86377] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Park2tm1Shn, Melt Curve Analysis
Park2tm1Shn, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Goldberg MS; Fleming SM; Palacino JJ; Cepeda C; Lam HA; Bhatnagar A; Meloni EG; Wu N; Ackerson LC; Klapstein GJ; Gajendiran M; Roth BL; Chesselet MF; Maidment NT; Levine MS; Shen J. 2003. Parkin-deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neurons. J Biol Chem 278(44):43628-35. [PubMed: 12930822] [MGI Ref ID J:86377]
Additional References
Park2tm1Shn relatedBerthet A; Bezard E; Porras G; Fasano S; Barroso-Chinea P; Dehay B; Martinez A; Thiolat ML; Nosten-Bertrand M; Giros B; Baufreton J; Li Q; Bloch B; Martin-Negrier ML. 2012. L-DOPA Impairs Proteasome Activity in Parkinsonism through D1 Dopamine Receptor. J Neurosci 32(2):681-91. [PubMed: 22238104] [MGI Ref ID J:179902]
Frank-Cannon TC; Tran T; Ruhn KA; Martinez TN; Hong J; Marvin M; Hartley M; Trevino I; O'Brien DE; Casey B; Goldberg MS; Tansey MG. 2008. Parkin deficiency increases vulnerability to inflammation-related nigral degeneration. J Neurosci 28(43):10825-34. [PubMed: 18945890] [MGI Ref ID J:140159]
Kao SY. 2009. Regulation of DNA repair by parkin. Biochem Biophys Res Commun 382(2):321-5. [PubMed: 19285961] [MGI Ref ID J:147872]
Kim KY; Stevens MV; Akter MH; Rusk SE; Huang RJ; Cohen A; Noguchi A; Springer D; Bocharov AV; Eggerman TL; Suen DF; Youle RJ; Amar M; Remaley AT; Sack MN. 2011. Parkin is a lipid-responsive regulator of fat uptake in mice and mutant human cells. J Clin Invest 121(9):3701-12. [PubMed: 21865652] [MGI Ref ID J:178238]
Kitada T; Pisani A; Karouani M; Haburcak M; Martella G; Tscherter A; Platania P; Wu B; Pothos EN; Shen J. 2009. Impaired dopamine release and synaptic plasticity in the striatum of parkin-/- mice. J Neurochem 110(2):613-21. [PubMed: 19457102] [MGI Ref ID J:150857]
Lee Y; Lee HY; Hanna RA; Gustafsson AB. 2011. Mitochondrial autophagy by Bnip3 involves Drp1-mediated mitochondrial fission and recruitment of Parkin in cardiac myocytes. Am J Physiol Heart Circ Physiol 301(5):H1924-31. [PubMed: 21890690] [MGI Ref ID J:178330]
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]
Palacino JJ; Sagi D; Goldberg MS; Krauss S; Motz C; Wacker M; Klose J; Shen J. 2004. Mitochondrial dysfunction and oxidative damage in parkin-deficient mice. J Biol Chem 279(18):18614-22. [PubMed: 14985362] [MGI Ref ID J:89508]
Rosen KM; Veereshwarayya V; Moussa CE; Fu Q; Goldberg MS; Schlossmacher MG; Shen J; Querfurth HW. 2006. Parkin protects against mitochondrial toxins and beta-amyloid accumulation in skeletal muscle cells. J Biol Chem 281(18):12809-16. [PubMed: 16517603] [MGI Ref ID J:112711]
Zhang C; Lin M; Wu R; Wang X; Yang B; Levine AJ; Hu W; Feng Z. 2011. Parkin, a p53 target gene, mediates the role of p53 in glucose metabolism and the Warburg effect. Proc Natl Acad Sci U S A 108(39):16259-64. [PubMed: 21930938] [MGI Ref ID J:177137]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, homozygous mice may be bred together. Mating System Homozygote x Homozygote (Female x Male) 01-JUL-08 Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Live Mice
Price (US dollars $) Gender Genotypes Provided Individual Mouse $172.00 Female or Male Homozygous for Park2tm1Shn
Pairs /Price (US dollars $) Pair Genotype $344.00 Homozygous for Park2tm1Shn x Homozygous for Park2tm1Shn Standard Supply
Repository-Live. The Repository Strains represent 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. We treat orders for these strains 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 |
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Live Mice
Price (US dollars $) Gender Genotypes Provided Individual Mouse $223.60 Female or Male Homozygous for Park2tm1Shn
Pairs /Price (US dollars $) Pair Genotype $447.20 Homozygous for Park2tm1Shn x Homozygous for Park2tm1Shn Standard Supply
Repository-Live. The Repository Strains represent 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. We treat orders for these strains 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. The Repository Strains represent 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. We treat orders for these strains 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.
General Supply Notes
- This strain is included in the Induced Mutant Resource Colony collection.
- Genomic DNA is available for this strain from the Mouse DNA Resource.
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.Ordering Information
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