Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Generation N22 (20-DEC-07)   Donating 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

Strains carrying other alleles of Park2

007587

129S-Park2tm1Rpa/J

View Strains carrying other alleles of Park2     (1 strain)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

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).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Park2^tm1Shn/Park2^tm1Shn

        involves: 129S4/SvJae

• behavior/neurological phenotype
• impaired coordination (MGI Ref ID J:86377)
  • poorer performance in various measures of motor performance
  • rotarod performance was normal
• nervous system phenotype
• abnormal nervous system electrophysiology (MGI Ref ID J:86377)
  • higher currents are required in striatal neurons to trigger synaptic response
• increased dopamine level (MGI Ref ID J:86377)
  • higher than normal levels of dopamine in the striatum

View Research Applications

Research Applications

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

Neurobiology Research
Parkinson's Disease (Park2 (parkin) mutants)
Parkinson's Disease

Genes & Alleles

Gene & Allele Information

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

Fluorescent Proteins (Generic GFP), STD PCR, vers. 1
Park2^tm1Shn, MCA, vers. 2
Park2^tm1Shn, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

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

Park2^tm1Shn related

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]

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]

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)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

The Jackson Laboratory's Genotype Promise

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 and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.