Overview

These RAG-2^fl mice harbor loxP sites flanking the entire coding region of the Rag2 (recombination activating gene 2) locus. When bred to mice that express Cre recombinase, the resulting offspring will have exon 3 deleted in the cre-expressing tissue(s). These RAG-2^fl may be useful in generating conditional mutations for studying the role of RAG-2 in B and T cell development (including cancer and toxicology research as a xenograft/transplant host), T and B cell receptor (V(D)J) recombination, hematopoiesis, hematology, immunology, and inflammation research.

Donating Investigator

IMR Colony, The Jackson Laboratory

Genetic overview

Genetic Background	Generation

Rag2^tm1Cgn

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), No functional change)	Rag2	recombination activating gene 2

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Research Applications

Research Tools
Virology Research
Internal/Organ Research
Immunology, Inflammation and Autoimmunity Research
Developmental Biology Research
Hematological Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for the RAG-2^fl allele are viable and fertile, with loxP sites flanking exon 3 of the targeted gene. When bred to mice that express Cre recombinase, the resulting offspring will have this region (coding for the entire RAG-2 protein) deleted in the cre-expressing tissue(s). These RAG-2^fl mice may be useful in generating conditional mutations for studying the role of RAG-2 in B and T cell development (including cancer and toxicology research as a xenograft/transplant host), T and B cell receptor (V(D)J) recombination, hematopoiesis, hematology, immunology, and inflammation research.

For example, when bred to a strain with inducible Cre recombinase expression in liver and lymphocytes (see Stock No. 003556), this mutant mouse strain may be useful in studies of B and T cell development.

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. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting vector was designed to insert a loxP-flanked neomycin resistance gene on one side, and a third loxP site on the other side of exon 3 of the targeted gene. This construct was electroporated into C57BL/6-derived Bruce-4 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a cre-expressing vector to remove the selection cassette. ES cells in which the neomycin resistance cassette was deleted (leaving a single loxP site upstream, and a single loxP downstream of exon 3) were injected into recipient blastocysts. Chimeric males were bred with C57BL/6 females to generate RAG-2^fl mice. These RAG-2^fl mice were bred with transgenic mice on mixed genetic background, and then bred with mutant mice on a C57BL/6 genetic background for 8 generations. The donating investigator reports that both the transgene and other mutant gene were bred out of these RAG-2^fl mice prior to arrival at The Jackson Laboratory (as Stock No. 008309). Upon arrival, some mice were backcrossed to BALB/cByJ (Stock No. 001026) using a marker-assisted approach to generate this congenic strain (Stock No. 008338).

Control Suggestions

001026 BALB/cByJ

Additional Information

Considerations for Choosing Controls

Selected References

Hao Z; Rajewsky K. 2001. Homeostasis of peripheral b cells in the absence of b cell influx from the bone marrow. J Exp Med 194(8):1151-64PubMed: 11602643 MGI: J:72214

View All References

Genetics

Rag2^tm1Cgn

Allele Symbol: Rag2^tm1Cgn

Allele Name	targeted mutation 1, University of Cologne
Allele Type	Targeted (Conditional ready (e.g. floxed), No functional change)
Allele Synonym(s)	RAG-2^fl
Gene Symbol and Name	Rag2, recombination activating gene 2
Gene Synonym(s)
Strain of Origin	B6.Cg-Thy1^a
Chromosome	2
Molecular Note	LoxP sites were inserted to flank the coding region of the gene. The inserted sites had no effect on the normal function of the gene.
Mutations Made By	Klaus Rajewsky, Max Delbruck Centre for Molecular Medicine

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Research Tools
- Cre-lox System
  - loxP-flanked Sequences
- Immunology, Inflammation and Autoimmunity Research
  - T cell deficiency
  - T cell deficiency, xenograft/transplant host
  - B and T cell deficiency
  - B cell deficiency
  - T Cell Receptor Deficiency
- Toxicology Research
  - B and T cell deficiency, xenograft transplant host
  - xenograft/transplant host
- Cancer Research
  - B cell deficiency
  - T cell deficiency
  - B and T cell deficiency, xenograft/transplant host
- Hematological Research
Virology Research
- B and T Cell Deficiency
Internal/Organ Research
- Thymus Defects
  - B and T cell deficient
- Lymphoid Tissue Defects
  - B and T cell deficiency
  - T cell deficiency
Immunology, Inflammation and Autoimmunity Research
- T Cell Receptor Signaling Defects
  - B and T cell deficiency
  - B and T cell deficiency, xenograft/transplant host
- Autoimmunity
  - B and T cell deficiency
  - B cell deficiency
- Inflammation
  - B and T cell deficiency
- Immunodeficiency
  - B cell deficiency
  - T cell deficiency
  - B and T cell deficiency
  - B cell defects
- Lymphoid Tissue Defects
  - B and T cell deficiency
  - hematopoietic development
Developmental Biology Research
- Lymphoid Tissue Defects
  - hematopoietic defects
- Internal/Organ Defects
  - hematopoietic defects
Hematological Research
- Hematopoietic Defects
- Immunological Defects
  - B and T cell deficiency

Mammalian Phenotype Terms by Genotype

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

Genotype: Rag2^tm1Cgn/Rag2^tm1.1Cgn Tg(Mx1-cre)1Cgn/0
involves: C57BL/6 * CBA

hematopoietic system phenotype

abnormal B cell activation
- Normal - B cells do not have this activated phenotype when Cre is induced in mice 8-10 weeks of age
- peripheral B cells have an activated phenotype in mice that have Cre expression induced at birth
- the activated phenotype include larger cell size and increased expression of CD25, CD69, CD86 and MHC-II when analyzed at 8 weeks of age

absent immature B cells
- the IgM⁺HSA^high immature B cell compartment in the spleen is absent two weeks after induction of Cre expression in mice 8-10 weeks old

absent pre-B cells
- pre-B cells are absent in the bone marrow of mice two weeks after induction of Cre expression in mice 8-10 weeks old

arrested B cell differentiation
- B cell development is arrested at the pro-B cell stage two weeks after induction of Cre expression in mice 8-10 weeks old

arrested T cell differentiation
- T cell development is arrested at the pro-T cell stage two weeks after induction of Cre expression in mice 8-10 weeks old

decreased follicular B cell number
- the number of follicular B cells in the spleen decline slowly after induction of Cre expression in mice 8-10 weeks old with a half-life of 134 days

decreased marginal zone B cell number
- Normal - marginal zone B cell numbers are normal when Cre-induction occurs in mice 8 to 10 weeks of age
- marginal zone B cells are decreased in number by 75% when Cre-induction occurs at birth
- the number of marginal zone B cells increases slightly with age but remains well below normal levels

decreased mature B cell number
- mature B cell numbers are reduced to 32% in the spleen 17 weeks after Cre induction and remain at this level for at least one year
- mature B cell numbers in lymph nodes drop to 58% of normal 10 weeks after Cre induction, and continue to drop to 11% of normal 17 weeks after Cre induction
- mature B cell numbers remain at 11% of normal between 17 and 54 weeks after induction of Cre expression
- the number of mature B cells in the bone marrow drop by half within two weeks of induction of Cre expression in mice 8-10 weeks old and then decline slowly over the next year with a half-life of 156 days
- the number of mature B cells in the spleen is reduced by 67% two weeks after Cre induction
- when Cre is induced in neonates, mature B cells numbers are 10- to 30- fold below normal

increased plasma cell number
- the total number of IgM secreting plasma cells found in the spleen is 3- to 4- fold larger in mice where Cre induction is induced at birth than in controls

immune system phenotype

abnormal B cell activation
- Normal - B cells do not have this activated phenotype when Cre is induced in mice 8-10 weeks of age
- peripheral B cells have an activated phenotype in mice that have Cre expression induced at birth
- the activated phenotype include larger cell size and increased expression of CD25, CD69, CD86 and MHC-II when analyzed at 8 weeks of age

absent immature B cells
- the IgM⁺HSA^high immature B cell compartment in the spleen is absent two weeks after induction of Cre expression in mice 8-10 weeks old

absent pre-B cells
- pre-B cells are absent in the bone marrow of mice two weeks after induction of Cre expression in mice 8-10 weeks old

arrested B cell differentiation
- B cell development is arrested at the pro-B cell stage two weeks after induction of Cre expression in mice 8-10 weeks old

arrested T cell differentiation
- T cell development is arrested at the pro-T cell stage two weeks after induction of Cre expression in mice 8-10 weeks old

decreased follicular B cell number
- the number of follicular B cells in the spleen decline slowly after induction of Cre expression in mice 8-10 weeks old with a half-life of 134 days

decreased marginal zone B cell number
- Normal - marginal zone B cell numbers are normal when Cre-induction occurs in mice 8 to 10 weeks of age
- marginal zone B cells are decreased in number by 75% when Cre-induction occurs at birth
- the number of marginal zone B cells increases slightly with age but remains well below normal levels

decreased mature B cell number
- mature B cell numbers are reduced to 32% in the spleen 17 weeks after Cre induction and remain at this level for at least one year
- mature B cell numbers in lymph nodes drop to 58% of normal 10 weeks after Cre induction, and continue to drop to 11% of normal 17 weeks after Cre induction
- mature B cell numbers remain at 11% of normal between 17 and 54 weeks after induction of Cre expression
- the number of mature B cells in the bone marrow drop by half within two weeks of induction of Cre expression in mice 8-10 weeks old and then decline slowly over the next year with a half-life of 156 days
- the number of mature B cells in the spleen is reduced by 67% two weeks after Cre induction
- when Cre is induced in neonates, mature B cells numbers are 10- to 30- fold below normal

increased plasma cell number
- the total number of IgM secreting plasma cells found in the spleen is 3- to 4- fold larger in mice where Cre induction is induced at birth than in controls

Genotype: Rag2^tm1Cgn/Rag2^tm1Cgn
C57BL/6-Rag2

normal phenotype

no abnormal phenotype detected
- Normal - B cell lymphopoiesis in the bone marrow is normal
- Normal - the number of B cells found in circulation is comparable to that of wild-type mice

References

Hao Z; Rajewsky K. 2001. Homeostasis of peripheral b cells in the absence of b cell influx from the bone marrow. J Exp Med 194(8):1151-64PubMed: 11602643 MGI: J:72214

Additional - Rag2^tm1Cgn related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Breeding Considerations

Mutant mice were bred to BALB/cByJ (Stock No. 001026) using a marker-assisted approach to establish this congenic strain. When maintaining the live congenic colony, homozygous mice may be bred together.
- Additional Breeding and Husbandry Support
Citation
When using the CByJ.B6(Cg)-Rag2^tm1Cgn/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008338 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
	Heterozygous for Rag2<tm1Cgn>

Related Products and Services

Frozen Mouse Embryo	CByJ.B6(Cg)-Rag2<tm1Cgn>/J	$2595.00
Frozen Mouse Embryo	CByJ.B6(Cg)-Rag2<tm1Cgn>/J	$2595.00
Frozen Mouse Embryo	CByJ.B6(Cg)-Rag2<tm1Cgn>/J	$3373.50
Frozen Mouse Embryo	CByJ.B6(Cg)-Rag2<tm1Cgn>/J	$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.

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Questions about Terms of Use

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Rag2tm1Cgn

Allele Symbol: Rag2tm1Cgn

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Rag2tm1Cgn/Rag2tm1.1Cgn Tg(Mx1-cre)1Cgn/0involves: C57BL/6 * CBA

hematopoietic system phenotype

immune system phenotype

Genotype: Rag2tm1Cgn/Rag2tm1CgnC57BL/6-Rag2

normal phenotype

References

Additional - Rag2tm1Cgn 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

Rag2^tm1Cgn

Allele Symbol: Rag2^tm1Cgn

Genotype: Rag2^tm1Cgn/Rag2^tm1.1Cgn Tg(Mx1-cre)1Cgn/0
involves: C57BL/6 * CBA

Genotype: Rag2^tm1Cgn/Rag2^tm1Cgn
C57BL/6-Rag2

Additional - Rag2^tm1Cgn related