Overview

Also Known As:Parkin -/-DJ-1-/-Gpx1-/-

This triple knockout strain is useful in studies of dopaminergic neuron physiology, regulation of striatal dopamine and serotonin, and Parkinson's disease.

Donating Investigator

Matthew Goldberg, University of Texas Southwestern Medical Center at Dallas

Genetic overview

Genetic Background	Generation

Prkn^tm1Shn

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Prkn	parkin RBR E3 ubiquitin protein ligase

Park7^tm1Shn

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Park7	Parkinson disease (autosomal recessive, early onset) 7

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Gpx1	glutathione peroxidase 1

Research Applications

Neurobiology Research
Research Tools

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

In the brains of patients with Parkinson's disease, the antioxidant enzyme glutathione peroxidase 1 activity level is diminished. Mutations in human PARK7 and PARK2 resulting loss of function have been linked to types of autosomal recessive Parkinson's disease. These mice carry targeted mutations for the Park7, Gpx1 and Park2 genes.
Mice that are homozygous for all 3 of the targeted mutations are viable and fertile.
In triple mutant mice, 12 to 18 months of age, striatal dopamine and serotonin levels are elevated, but with normal nigral neuron numbers. Parkin^-/- DJ-1^-/- Gpx1^-/- exhibit enhanced motor behavior and are able to outperform wildtype controls in the rotarod test.
During backcrossing, the Y chromosome may not have been fixed to the C57BL/6J genetic background.

Development

For the Park7 allele, a targeting vector designed by Dr. Jie Shen (Brigham
& Women's Hospital, Harvard University) containing a PGK-neomycin cassette was used to disrupt exon 2. The construct was electroporated into (C57BL/6 x 129)F1 derived MKV6.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were tested for germline transmission.
The mice were backcrossed to C57BL/6J for 10 generations.

For the Gpx1^tm1Ysh allele, a targeting vector designed by Dr. Ye-Shih Ho (Wayne State University) containing a NEO cassette was used to disrupt exon 2. The construct was electroporated into 129 derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were tested for germline transmission.
The mice were crossed for approximately 6 generations to C57BL/6. Dr. Matthew Goldberg obtained the mice and backcrossed them to C57BL/6J for 3 or 4 generations. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6 genetic background.

For the Park2 allele, a targeting vector designed by a targeting vector designed by Dr. Jie Shen (Brigham & Women's Hospital, Harvard University) containing an in-frame EGFP coding sequence (followed by translation and transcription termination sequences and a PGK-neomycin cassette) was used to disrupt most of exon 3. The construct was electroporated into the 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were tested for germline transmission. The mice were backcrossed to C57BL/6J for 10 generations.

To generate this triple mutant strain, the Park7 and Park2 knockout lines were bred and intercrossed to obtain double knockout mice. The double knockout mice were then crossed to the Gpx1 knockout mice for 2 generations, and then intercrossed to obtain mice homozygous for all 3 alleles, Parkin^-/- DJ-1^-/- Gpx1^-/- (See SNP note below). Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While 26 of the 27 markers throughout the genome suggested a C57BL/6 genetic background, 2 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Hennis MR; Marvin MA; Taylor CM 2nd; Goldberg MS. 2013. Surprising behavioral and neurochemical enhancements in mice with combined mutations linked to Parkinson's disease. Neurobiol Dis 62C:113-123PubMed: 24075852 MGI: J:202221

View All References

Genetics

Prkn^tm1Shn

Allele Symbol: Prkn^tm1Shn

Allele Name	targeted mutation 1, Jie Shen
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Park2^tm1Shn; parkin -
Gene Symbol and Name	Prkn, parkin RBR E3 ubiquitin protein ligase
Gene Synonym(s)
Strain of Origin	129S4/SvJae
Chromosome	17
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.
Mutations Made By	Jie Shen, Harvard Med Sch/Brigham Women's Hosp

Park7^tm1Shn

Allele Symbol: Park7^tm1Shn

Allele Name	targeted mutation 1, Jie Shen
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	DJ-1^-
Gene Symbol and Name	Park7, Parkinson disease (autosomal recessive, early onset) 7
Gene Synonym(s)
Strain of Origin	(C57BL/6 x 129)F1
Chromosome	4
Molecular Note	Exon 2 was replaced with a pgk-neo cassette. Western blot failed to detect protein in mutant mice.
Mutations Made By	Jie Shen, Harvard Med Sch/Brigham Women's Hosp

Gpx1^tm1Ysh

Allele Symbol: Gpx1^tm1Ysh

Allele Name	targeted mutation 1, Ye-Shih Ho
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Gpx1-; GPX1 KO; GpX-1 KO; GSHPx-1-deficient
Gene Symbol and Name	Gpx1, glutathione peroxidase 1
Gene Synonym(s)
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Chromosome	9
Molecular Note	Insertion of a neomycin resistance cassette disrupted exon 2 of the gene. Northern blots of total RNA isolated from brain, heart, kidney, liver, and lung of homozygous mutant mice showed no detectable transcript of the targeted gene when probed with an a gene-specific cDNA probe.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Neurobiology Research
- Parkinson's Disease
Research Tools
- Neurobiology Research

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Gpx1^tm1Ysh/Gpx1^tm1Ysh Prkn^tm1Shn/Prkn^tm1Shn Park7^tm1Shn/Park7^tm1Shn
B6.Cg-Park7 Gpx1 Prkn

behavior/neurological phenotype

impaired coordination
- increased latency to fall (rotarod test) observed at 12 and 18 months of age as compared to controls

homeostasis/metabolism phenotype

increased dopamine level
- striatal dopamine levels are significantly elevated at 6, 12 and 18 months of age, however, dopamine turnover is similar to controls

increased serotonin level
- striatal serotonin levels are increased at 12 months of age, however, serotonin turnover is similar to controls

nervous system phenotype

increased serotonin level
- striatal serotonin levels are increased at 12 months of age, however, serotonin turnover is similar to controls

References

Hennis MR; Marvin MA; Taylor CM 2nd; Goldberg MS. 2013. Surprising behavioral and neurochemical enhancements in mice with combined mutations linked to Parkinson's disease. Neurobiol Dis 62C:113-123PubMed: 24075852 MGI: J:202221

Additional - Gpx1^tm1Ysh related

Additional - Park7^tm1Shn related

Additional - Prkn^tm1Shn related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Park7
- Standard PCR:Gpx1alternate1
- Standard PCR:Park2
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred as homozygotes for each targeted mutation.
- Additional Breeding and Husbandry Support
Citation
When using the Parkin -/-DJ-1-/-Gpx1-/- mouse strain in a publication, please cite the originating article(s) and include JAX stock #023968 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Homozygous for Park7<tm1Shn>, Homozygous for Gpx1<tm1Ysh>, Homozygous for Park2<tm1Shn>

Related Products and Services

Frozen Mouse Embryo	B6.Cg-Park7<tm1Shn> Gpx1<tm1Ysh> Prkn<tm1Shn> Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6.Cg-Park7<tm1Shn> Gpx1<tm1Ysh> Prkn<tm1Shn> Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6.Cg-Park7<tm1Shn> Gpx1<tm1Ysh> Prkn<tm1Shn> Frozen Embryos	$3373.50
Frozen Mouse Embryo	B6.Cg-Park7<tm1Shn> Gpx1<tm1Ysh> Prkn<tm1Shn> Frozen Embryos	$3373.50

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

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Licensing Information

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Also Known As:Parkin -/-DJ-1-/-Gpx1-/-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Prkntm1Shn

Allele Symbol: Prkntm1Shn

Park7tm1Shn

Allele Symbol: Park7tm1Shn

Gpx1tm1Ysh

Allele Symbol: Gpx1tm1Ysh

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Gpx1tm1Ysh/Gpx1tm1Ysh Prkntm1Shn/Prkntm1Shn Park7tm1Shn/Park7tm1ShnB6.Cg-Park7 Gpx1 Prkn

behavior/neurological phenotype

homeostasis/metabolism phenotype

nervous system phenotype

References

Additional - Gpx1tm1Ysh related

Additional - Park7tm1Shn related

Additional - Prkntm1Shn related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Prkn^tm1Shn

Allele Symbol: Prkn^tm1Shn

Park7^tm1Shn

Allele Symbol: Park7^tm1Shn

Gpx1^tm1Ysh

Allele Symbol: Gpx1^tm1Ysh

Genotype: Gpx1^tm1Ysh/Gpx1^tm1Ysh Prkn^tm1Shn/Prkn^tm1Shn Park7^tm1Shn/Park7^tm1Shn
B6.Cg-Park7 Gpx1 Prkn

Additional - Gpx1^tm1Ysh related

Additional - Park7^tm1Shn related

Additional - Prkn^tm1Shn related