Overview

These Park7 knockout mice exhibit non-progressive hypokinesia, progressive gait abnormalities, decreased grip strength, loss of body weight and may be useful in studies of Parkinson's disease.

Donating Investigator

Huaibin Cai, National Institutes of Health / National Institute on Aging (NIH/NIA)

Genetic overview

Genetic Background	Generation

Park7^tm1Cai

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

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Research Applications

Neurobiology Research

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Details

Detailed Description

Homozygote: Mice that are homozygous for the targeted mutation exhibit non-progressive hypokinesia at 5 months of age and progressive gait abnormalities (stride uniformity, hind base displacement) beginning at two months of age. Mice over a year old develop decreased grip strength, loss of body weight and severe gait abnormalities. Although early onset progressive motor deficits occur in these mice, no pathological changes are observed in the nigrostriatal system, spinal motor system or muscles. This mutant mouse strain may be useful in studies of Parkinson's disease.

Heterozygote: Not evaluated

Development

A targeting vector containing a neomycin resistance cassette was used to disrupt exon 2. The construct was electroporated into 129X1/SvJ derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice and maintained by intercross. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

Control Suggestions

Approximate Controls

101045 B6129SF2/J

Additional Information

Considerations for Choosing Controls

Selected References

Chandran JS; Lin X; Zapata A; Hoke A; Shimoji M; Moore SO; Galloway MP; Laird FM; Wong PC; Price DL; Bailey KR; Crawley JN; Shippenberg T; Cai H. 2008. Progressive behavioral deficits in DJ-1-deficient mice are associated with normal nigrostriatal function. Neurobiol Dis 29(3):505-14PubMed: 18187333 MGI: J:141628

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Genetics

Park7^tm1Cai

Allele Symbol: Park7^tm1Cai

Allele Name	targeted mutation 1, Hubaibin Cai
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)
Gene Symbol and Name	Park7, Parkinson disease (autosomal recessive, early onset) 7
Gene Synonym(s)
Strain of Origin	129X1/SvJ
Chromosome	4
Molecular Note	The first coding exon was replaced with a selection marker flanked with loxp sites. QPCR and Western blot analysis confirmed the absence of gene products.

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Parkinson's disease 7

Research Areas By Phenotype

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

Neurobiology Research
- Ataxia (Movement) Defects
- Parkinson's Disease
  - Park7 (DJ-1) mutants

Mammalian Phenotype Terms by Genotype

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

Genotype: Park7^tm1Cai/Park7^tm1Cai
involves: 129X1/SvJ * C57BL/6

behavior/neurological phenotype

short stride length
- dopamine treatment failed to increase stride length as it did for wild-type mice
- two-year old mice have a mean decrease in stride length with a mean of 5.35 cm vs. 5.9 for controls
- Normal - this defect in stride length is not observed in 2-month mice

abnormal gait
- two month old mice have defects in stride uniformity and hind base displacement
- defects are more severe in two year old mice

abnormal motor learning
- 16-month old mice have enhanced motor learning over 3 days with 62.3% increase in latency time to fall compared to just a 34.6% increase for wild-type controls

decreased grip strength
- mice at 16 months of age, but not 2 months of age, have a significant decrease in foregrip strength

hypoactivity
- mice at 5 and 14 months of age have decreased activity

growth/size/body region phenotype

weight loss
- Normal - mice weigh less than controls starting around 1 year in age

References

Chandran JS; Lin X; Zapata A; Hoke A; Shimoji M; Moore SO; Galloway MP; Laird FM; Wong PC; Price DL; Bailey KR; Crawley JN; Shippenberg T; Cai H. 2008. Progressive behavioral deficits in DJ-1-deficient mice are associated with normal nigrostriatal function. Neurobiol Dis 29(3):505-14PubMed: 18187333 MGI: J:141628

Additional - Park7^tm1Cai related

Technical Support

CONTACT TECHNICAL SUPPORT

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

While maintaining a live colony, these mice are bred as homozygotes.
- Additional Breeding and Husbandry Support
Citation
When using the B6;129X1-Park7^tm1Cai/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #32090 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

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

See MMRRC for Additional Conditions of Distribution

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Park7tm1Cai

Allele Symbol: Park7tm1Cai

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Park7tm1Cai/Park7tm1Caiinvolves: 129X1/SvJ * C57BL/6

behavior/neurological phenotype

growth/size/body region phenotype

References

Additional - Park7tm1Cai related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Park7^tm1Cai

Allele Symbol: Park7^tm1Cai

Genotype: Park7^tm1Cai/Park7^tm1Cai
involves: 129X1/SvJ * C57BL/6

Additional - Park7^tm1Cai related