Overview

Also Known As:MSH2^-

A percentage of Msh2 (mutS homolog 2) knock-out mice develop lymphoid tumors containing microsatellite instabilities by two months of age. These mice may be useful for studies of the pathogenesis of cancer and as a screen for carcinogenic and anti-cancer agents.

Donating Investigator

Dr. Tak Mak, University Health Network / University of Toronto

Genetic overview

Genetic Background	Generation

Msh2^tm1Mak

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Msh2	mutS homolog 2

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Research Applications

Cancer Research
Research Tools

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Details

Detailed Description

The Msh2 (mutS homolog 2) gene encodes a homolog of the E. coli mismatch repair gene mutS. Mutations in Msh2 are associated with hereditary nonpolyposis colon cancer (HNPCC). Mice homozygous for the knockout allele are viable and fertile. Beginning at two months of age, some MSH2^- mice develop lymphoid tumors containing microsatellite instabilities. Five the six mice diagnosed with lymphoblastic lymphoma exhibit widely disseminated lymphoma in the spleen, liver and thymus. Mice that develop lymphomas die by 5 months of age.
These mice may be useful for studies of the pathogenesis of cancer and as a screen for carcinogenic and anti-cancer agents.

Development

A targeting vector containing a PGK-neomycin cassette, in reverse orientation, was used to disrupt an exon that corresponds to human exon 11 resulting in the deletion of 68 base pairs. The construct was electroporated into 129P2/OlaHsd derived E14K embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were bred to C57BL/6J to achieve germline transmission. The mice were then backcrossed to C57BL/6 for at least 9 generations. Upon arrival, sperm was cryopreserved. To establish a live colony, an aliquot of frozen sperm is used to fertilize C57BL/6J.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Reitmair AH; Schmits R; Ewel A; Bapat B; Redston M; Mitri A; Waterhouse P; Mittrucker HW; Wakeham A; Liu B; Thomason A; Griesser H; Gallinger S; Ballhausen WG; Fishel R; Mak TW. 1995. MSH2 deficient mice are viable and susceptible to lymphoid tumours. Nat Genet 11(1):64-70PubMed: 7550317 MGI: J:28397

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Genetics

Msh2^tm1Mak

Allele Symbol: Msh2^tm1Mak

Allele Name	targeted mutation 1, Tak W Mak
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	MSH2-
Gene Symbol and Name	Msh2, mutS homolog 2
Gene Synonym(s)
Strain of Origin	129P2/OlaHsd
Chromosome	17
Molecular Note	A neomycin resistance cassette was inserted in an antisense orientation in an exon of the gene that corresponded to exon 11 of the human gene, resulting in the deletion of 68 bp (1959 - 2026). Western blots of protein extracts from tail fibroblasts of homozygous mutant mice showed no detectable protein expressed for the targeted gene.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Cancer Research
- Increased Tumor Incidence
  - Lymphomas
Research Tools
- Cancer Research
  - genes regulating lymphoma development

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Msh2^tm1Mak/Msh2^tm1Mak
involves: 129P2/OlaHsd * C57BL/6J

mammalian phenotype

immune system phenotype
- Normal - no gross abnormalities were seen

mortality/aging

premature death
- between 2 and 5 months of age, due to tumor-related illness

neoplasm

increased lymphoma incidence
- increased incidence of metastasizing lymphoma, beginning ~2 months of age, incomplete penetrance

References

Reitmair AH; Schmits R; Ewel A; Bapat B; Redston M; Mitri A; Waterhouse P; Mittrucker HW; Wakeham A; Liu B; Thomason A; Griesser H; Gallinger S; Ballhausen WG; Fishel R; Mak TW. 1995. MSH2 deficient mice are viable and susceptible to lymphoid tumours. Nat Genet 11(1):64-70PubMed: 7550317 MGI: J:28397

Additional - Msh2^tm1Mak related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Msh2
- Standard PCR:Generic Neo
- Probe:Generic Neo
- 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 MSH2^- mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #42057 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

Also Known As:MSH2-

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Msh2tm1Mak

Allele Symbol: Msh2tm1Mak

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Msh2tm1Mak/Msh2tm1Makinvolves: 129P2/OlaHsd * C57BL/6J

mammalian phenotype

mortality/aging

neoplasm

References

Additional - Msh2tm1Mak 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

Also Known As:MSH2^-

Msh2^tm1Mak

Allele Symbol: Msh2^tm1Mak

Genotype: Msh2^tm1Mak/Msh2^tm1Mak
involves: 129P2/OlaHsd * C57BL/6J

Additional - Msh2^tm1Mak related