Overview

Also Known As: Rag1 KO

Mice homozygous for Rag1^tm1Mom produce no mature T cells or B cells. The thymus in mutant mice is severely involuted. B cell and T cell development is apparently arrested at an early stage. These characteristics qualify this strain as a useful tool for HIV-1 studies and research involving human hematolymphoid cell engraftment or NOD diabetes pathogenesis.

Donating Investigator

Dr. Leonard D. Shultz, The Jackson Laboratory

Genetic overview

Genetic Background	Generation
	N10+N3f3 (2019-06-17 00:00:00)

Rag1^tm1Mom

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Rag1	recombination activating gene 1

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Research Applications

Immunology, Inflammation and Autoimmunity Research
Research Tools
Internal/Organ Research
Cancer Research
Hematological Research
Diabetes and Obesity Research

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Base Price

Starting at:

$236.78 Domestic price for female

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Details

Detailed Description

Mice homozygous for the Rag1^tm1Mom mutation produce no mature T cells or B cells. Their phenotype can be described as a "non-leaky" severe combined immune deficiency. (Prkdc^scid/Prkdc^scid) mice produce some B cells and IgM. NOD.129S7(B6)-Rag1^tm1Mom/J mice have no CD3⁺ or T cell receptor (TCR) alpha-beta positive cells. The thymus of the mutant mice is severely involuted. The thymocytes are CD8^-CD4^- and most are IL2 receptor positive. Neither the spleen nor bone marrow contain any IgM or IgD staining cells, indicating an absence of mature B cells. These and other data suggest that both B cell and T cell development have been arrested at an early stage. Macroscopically, the mutants are indistinguishable from heterozygotes or normal wildtype siblings. Notable differences between this strain and the NOD.CB17-Prkdc^scid/J strain (Stock No. 001303) include a longer life span due to delayed onset of lymphoma development, greater radioresistance and a complete absence of serum Ig. These characteristics qualify this strain as a useful tool for HIV-1 studies and research involving human hematolymphoid cell engraftment or NOD diabetes pathogenesis.

Development

The Rag1^tm1Mom mutant strain was developed by Dr. Peter Mombaerts in the laboratory of Dr. Susumu Tonegawa at the Center for Cancer Research, Massachusetts Institute of Technology. A replacement targeting vector with the Pgk-neo marker was used. Homologous recombination of the targeting vector resulted in a 1356 bp deletion in the 5' end of the coding sequence. The 129-derived AB1 ES cell line was used.

Control Suggestions

Additional control strains are available depending on the researchers needs.
001976 NOD/ShiLtJ

Additional Information

Considerations for Choosing Controls

Selected References

Shultz LD; Lang PA; Christianson SW; Gott B; Lyons B; Umeda S; Leiter E; Hesselton R; Wagar EJ; Leif JH; Kollet O; Lapidot T; Greiner DL. 2000. NOD/LtSz-Rag1null mice: An immunodeficient and radioresistant model for engraftment of human hematolymphoid cells, HIV infection, and adoptive transfer of NOD mouse diabetogenic T cells J Immunol 164(5):2496-507PubMed: 10679087 MGI: J:60800

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Genetics

Rag1^tm1Mom

Allele Symbol: Rag1^tm1Mom

Allele Name	targeted mutation 1, Peter Mombaerts
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Rag1^tm1Mom; targeted mutation 1, Peter Mombaerts
Gene Symbol and Name	Rag1, recombination activating gene 1
Gene Synonym(s)	Rag-1; RAG-1; RNF74; Rag-1
Site of Expression	expression is seen in bone marrow derived cell lines.
Strain of Origin	129S7/SvEvBrd-Hprt⁺
Chromosome	2
Molecular Note	A 1356 bp genomic fragment of the Rag1 gene, encoding the nuclear localization signal and the zinc-finger motif, was replaced by a neomycin cassette. A mutant transcript expressed from this allele was detected by Northern blot in bone marrow derived cell lines from homozygous mice.
Mutations Made By	Peter Mombaerts, Max Planck Research Unit for Neurogenetics

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Genotype: Rag1^tm1Mom related

Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - B and T cell deficiency
- T Cell Receptor Signaling Defects
  - B and T cell deficiency
- Inflammation
  - B and T cell deficiency
Research Tools
- Toxicology Research
  - xenograft/transplant host
- Cancer Research
  - B and T cell deficiency, xenograft/transplant host
Internal/Organ Research
- Lymphoid Tissue Defects
  - B and T cell deficiency
Cancer Research
- Toxicology
  - B and T cell deficiency, xenograft/transplant host
Hematological Research
- Immunological Defects
  - B and T cell deficiency

Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - B and T cell deficiency
Diabetes and Obesity Research
- Islet Transplantation Studies
- Type 1 Diabetes (IDDM) Analysis Strains
  - NOD Congenics with Mutations Affecting Immunocompetence

Mammalian Phenotype Terms by Genotype

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

Genotype: Rag1^tm1Mom/Rag1^tm1Mom
NOD.129S7(B6)-Rag1

hematopoietic system phenotype

decreased CD4-positive, alpha beta T cell number
- spleens of 8-11 week old mice are deficient in CD3+ CD4+ T cells

decreased CD8-positive, alpha-beta T cell number
- spleens of 8-11 week old mice are deficient in CD3+ CD8+ T cells

decreased immunoglobulin level
- no serum immunoglobulin is detected in 218-334 day old mice

decreased mature B cell number
- spleens of 8-11 week old mice are deficient in Igkappa+ B220+ T cells

impaired natural killer cell mediated cytotoxicity
- Background Sensitivity - poly I:C stimulated spleen cells exhibit low levels of NK cell cyotoxic activity in comparison to C57BL/6 homozygotes

increased granulocyte number
- numbers of granulocytes are increased in comparison to NOD controls

increased immature B cell number
- IgLkappa- B220+ immature B cell numbers are increased as compared to NOD controls

increased macrophage cell number
- numbers of macrophages are increased in comparison to NOD controls

increased NK cell number
- numbers of NK cells are increased in comparison to NOD controls

spleen hypoplasia
- nucleated spleen cells are reduced in 8-11 week old mice as compared to NOD control

immune system phenotype

abnormal level of surface class II molecules
- four to five-fold decrease in cells expressing I-A^g7 as compared to NOD control

decreased CD4-positive, alpha beta T cell number
- spleens of 8-11 week old mice are deficient in CD3+ CD4+ T cells

decreased CD8-positive, alpha-beta T cell number
- spleens of 8-11 week old mice are deficient in CD3+ CD8+ T cells

decreased immunoglobulin level
- no serum immunoglobulin is detected in 218-334 day old mice

decreased mature B cell number
- spleens of 8-11 week old mice are deficient in Igkappa+ B220+ T cells

impaired natural killer cell mediated cytotoxicity
- Background Sensitivity - poly I:C stimulated spleen cells exhibit low levels of NK cell cyotoxic activity in comparison to C57BL/6 homozygotes

increased granulocyte number
- numbers of granulocytes are increased in comparison to NOD controls

increased immature B cell number
- IgLkappa- B220+ immature B cell numbers are increased as compared to NOD controls

increased macrophage cell number
- numbers of macrophages are increased in comparison to NOD controls

increased NK cell number
- numbers of NK cells are increased in comparison to NOD controls

spleen hypoplasia
- nucleated spleen cells are reduced in 8-11 week old mice as compared to NOD control

References

Shultz LD; Lang PA; Christianson SW; Gott B; Lyons B; Umeda S; Leiter E; Hesselton R; Wagar EJ; Leif JH; Kollet O; Lapidot T; Greiner DL. 2000. NOD/LtSz-Rag1null mice: An immunodeficient and radioresistant model for engraftment of human hematolymphoid cells, HIV infection, and adoptive transfer of NOD mouse diabetogenic T cells J Immunol 164(5):2496-507PubMed: 10679087 MGI: J:60800

Additional References

Chen J; Gusdon AM; Piganelli J; Leiter EH; Mathews CE. 2011. mt-Nd2(a) Modifies resistance against autoimmune type 1 diabetes in NOD mice at the level of the pancreatic beta-cell. Diabetes 60(1):355-9PubMed: 20980458 MGI: J:170153
Maykel J; Liu JH; Li H; Shultz LD; Greiner DL; Houghton J. 2014. NOD-scidIl2rg (tm1Wjl) and NOD-Rag1 (null) Il2rg (tm1Wjl) : a model for stromal cell-tumor cell interaction for human colon cancer. Dig Dis Sci 59(6):1169-79PubMed: 24798995 MGI: J:227975

Additional - Rag1^tm1Mom related

Technical Support

Contact Technical Support

Genotyping Protocols
- MELT: Rag1^tm1MomAlternate1
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

The original B6,129S-Rag1^tm1Mom line was backcrossed to the NOD/LtSz strain background for ten generations. At the tenth generation, mice were intercrossed. They are now being maintained as homozygotes. These mice are severely immunodeficient so specific pathogen-free (SPF) conditions are recommended. Coat color expected from breeding: albino
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Homozygote
Appearance
- albino
  Related Genotype: Tyr^c/Tyr^c
Citation
When using the Rag1 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #003729 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX11 (Maximum)

Pricing & Availability

Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous for Rag1<tm1Mom>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

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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.

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.

Terms Of Use

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General Terms and Conditions

Questions about Terms of Use

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Licensing Information

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Email: TechTran@jax.org

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Also Known As: Rag1 KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Rag1tm1Mom

Allele Symbol: Rag1tm1Mom

Disease Terms

Research Areas By Genotype

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

Genotype: Rag1tm1Mom related

Mammalian Phenotype Terms by Genotype

Genotype: Rag1tm1Mom/Rag1tm1MomNOD.129S7(B6)-Rag1

hematopoietic system phenotype

immune system phenotype

References

Additional References

Additional - Rag1tm1Mom related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Appearance

Citation

Animal Health Reports

Live Mouse

Cryorecovery - Pricing

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

Rag1^tm1Mom

Allele Symbol: Rag1^tm1Mom

Genotype: Rag1^tm1Mom related

Genotype: Rag1^tm1Mom/Rag1^tm1Mom
NOD.129S7(B6)-Rag1

Additional - Rag1^tm1Mom related