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)   04-OCT-12 Species laboratory mouse Generation ?+F4 (14-FEB-13) Generation Definitions   Donating Investigator Raju Kucherlapati,   Brigham & Women's Hosp, Harvard Med Sch

Description
The Msh2^LoxP allele has loxP sites flanking exon 12 of the mutS homolog 2 (E. coli) [Msh2] gene. Homozygous Msh2^LoxP mice are viable and fertile with no observed abnormalities. When bred to mice that express Cre recombinase, the resulting offspring will have the sequences encoding a portion of the essential ATPase domain of MSH2 protein deleted in the cre-expressing tissue(s). These Msh2^LoxP mice may be useful in generating tissue-specific MSH2 deletions for studying DNA mismatch repair (single-nucleotide and insertion/deletion mismatches), as well as tumor development.

For example, when Msh2^LoxP mice are bred to a strain expressing Cre recombinase in embryonic tissues (EIIA-Cre; see Stock Nos. 003314 or 003724), the resulting mice with pan deletion of MSH2 exhibit high incidence of lymphoma.

Additionally, when Msh2^LoxP mice are bred to Villin-Cre mice (see Stock No. 004586 for example), the resulting mice with MSH2 mismatch repair function inactivated in the intestinal mucosa exhibit intestinal adenomas/adenocarcinomas and somatic Apc mutations at tumor initiation. This allows modeling of the intestinal cancer features of Lynch Syndrome because the lymphoma phenotype of pan MSH2 knockout mice is greatly diminished with tumorigenesis restricted predominantly to the intestinal tract.

Development
A targeting vector was designed to insert a loxP site and frt-flanked PGK-neo cassette upstream of exon 12, and a second loxP site downstream of exon 12 of the mutS homolog 2 (E. coli) [Msh2] gene. The donating investigator reports that the construct was electroporated into 129/Sv;C57BL/6J;SJL-derived WW6 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric males were bred with C57BL/6J females to establish the colony. To remove the frt-flanked PGK-neo cassette, the Msh2neo^{LoxP-FRT neo} mice were then bred to mice expressing FLPe recombinase (unknown genetic background; see Stock Nos. 005703 or 003800). The resulting Msh2^LoxP mice (with loxP site and single frt site remaining upstream of exon 12, and a second loxP site downstream of exon 12) were backcrossed to C57BL/6J mice for ten generations, and then bred together to generate homozygous mice prior to sending to The Jackson Laboratory Repository. Upon arrival, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Lynch Syndrome I   (MSH2) Mismatch Repair Cancer Syndrome; MMRCS   (MSH2) Muir-Torre Syndrome; MRTES   (MSH2)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

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

Msh2^tm2.1Rak/Msh2^tm2.1Rak

        involves: 129/Sv * C57BL/6 * C57BL/6J * SJL

• tumorigenesis
• *normal* tumorigenesis
  • mice do not develop lymphomas   (MGI Ref ID J:161577)

View Research Applications

Research Applications

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

Cancer Research
Chronic Myelogenous Leukemia
Increased Tumor Incidence
      Adenomas
      Adenomas: intestinal adenomas
      Lymphomas
      Other Tissues/Organs
      Other Tissues/Organs: GI tract (stomach, intestine, colon)
      Skin Cancers
Other
      DNA Repair
      tumor metastasis
Tumor Resistance
Tumor Suppressor Genes

Cell Biology Research
DNA Damage Response

Neurobiology Research
Cre-lox System
      loxP-flanked Sequences

Research Tools
Cancer Research
      Leukemia
      Mutation Rate Quantitation and Identification
      genes regulating lymphoma development
      tumor immunology
Cardiovascular Research
      Cre-lox System
Cre-lox System
      loxP-flanked Sequences
Developmental Biology Research
      Cre-lox System
Genetics Research
      Mutagenesis and Transgenesis: Cre-lox System

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Msh2tm2.1Rak
Allele Name		targeted mutation 2.1, Raju Kucherlapati
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		M2CKO; MSH2CKO; MSH2CKO pGKneo flipped ou; Msh2LoxP;
Mutation Made By		Raju Kucherlapati,   Brigham & Women's Hosp, Harvard Med Sch
Strain of Origin		STOCK 129/Sv and C57BL/6J and SJL
Gene Symbol and Name		Msh2, mutS homolog 2 (E. coli)
Chromosome		17
Gene Common Name(s)		AI788990; COCA1; FCC1; HNPCC; HNPCC1; LCFS2; expressed sequence AI788990;
Molecular Note		An frt flanked neo cassette with a 5' loxP site was inserted upstream of exon 12, and an additional loxP site was inserted downstream of exon 12. Flp mediated recombination removed the neo cassette leaving exon 12 floxed. [MGI Ref ID J:161577]

Genotyping

Genotyping Information

Genotyping Protocols

Msh2^tm2.1Rak, Standard PCR
Msh2^tm2.1Rak, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Kucherlapati MH; Lee K; Nguyen AA; Clark AB; Hou H Jr; Rosulek A; Li H; Yang K; Fan K; Lipkin M; Bronson RT; Jelicks L; Kunkel TA; Kucherlapati R; Edelmann W. 2010. An Msh2 conditional knockout mouse for studying intestinal cancer and testing anticancer agents. Gastroenterology 138(3):993-1002.e1. [PubMed: 19931261]  [MGI Ref ID J:161577]

Additional References

Msh2^tm2.1Rak related

Kovalenko M; Dragileva E; St Claire J; Gillis T; Guide JR; New J; Dong H; Kucherlapati R; Kucherlapati MH; Ehrlich ME; Lee JM; Wheeler VC. 2012. Msh2 acts in medium-spiny striatal neurons as an enhancer of CAG instability and mutant huntingtin phenotypes in Huntington's disease knock-in mice. PLoS One 7(9):e44273. [PubMed: 22970194]  [MGI Ref ID J:191886]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred together.
Mating System	Homozygote x Homozygote         (Female x Male)   04-OCT-12

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• 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.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

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.

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Terms of Use

Terms of Use

General Terms and Conditions

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