Overview

Also Known As:RAG-1^-

Mice homozygous for the Rag1^tm1Mom mutation produce no mature T cells or B cells, and data suggest that B cell and T cell development has been arrested at an early stage.

Donating Investigator

Peter Mombaerts, Max Planck Research Unit for Neurogenetics

Genetic overview

Genetic Background	Generation

Rag1^tm1Mom

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

View Genetics

Research Applications

Research Tools
Immunology, Inflammation and Autoimmunity Research
Internal/Organ Research
Cancer 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 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) (Prkdc^scid mice produce some B cells and IgM). They have no CD3⁺ or T cell receptor (TCR) alpha-beta positive cells. The thymus of the mutant mice contains 15 to 130 times fewer cells than heterozygous or wildtype siblings. 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 B cell and T cell development has been arrested at an early stage. Macroscopically, the mutants are indistinguishable from heterozygotes or normal wildtype siblings.

Control Suggestions

C57BL/6J mice provide only an approximate genetic match as this strain has been backcrossed only five generations.

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Mombaerts P; Iacomini J; Johnson RS; Herrup K; Tonegawa S; Papaioannou VE. 1992. RAG-1-deficient mice have no mature B and T lymphocytes. Cell 68(5):869-77PubMed: 1547488 MGI: J:1934

View All References

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 Phenotype

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

Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - B and T cell deficiency

Genotype: Rag1^tm1Mom related

Immunology, Inflammation and Autoimmunity Research
- Inflammation
  - B and T cell deficiency
- Immunodeficiency
  - B and T cell deficiency
- T Cell Receptor Signaling Defects
  - 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

Mammalian Phenotype Terms by Genotype

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

Genotype: Rag1^tm1Mom/Rag1^tm1Mom
involves: 129S7/SvEvBrd * CD-1

endocrine/exocrine gland phenotype

thymus hypoplasia
- thymus contains 15 to 300 times fewer cells than wild-type or heterozygous controls

immune system phenotype

abnormal B cell differentiation
- spleen and bone marrow lack mature B cells; B cells are IgM and IgD negative, and only 1/4 to 1/3 are B220-positive

abnormal immunoglobulin V(D)J recombination
- absence of V(D)J recombination

abnormal inguinal lymph node morphology
- stroma-like structure found in inguinal lymph nodes location, with few, if any, nonerythroid cells recoverable from this structure

abnormal T cell differentiation
- thymocyte development is arrested at an early stage; cells are larger than normal, and are CD3^-, TCR alphabeta-negative, CD8^- CD4^-

abnormal T cell morphology
- no mature T lymphocytes are seen in lymphoid organs
- thymocytes are larger in 4-, 5-, and 7-week old mutants than in controls

abnormal T cell receptor V(D)J recombination
- absence of V(D)J recombination

absent mature B cells
- no mature B lymphocytes are observed in lymphoid organs

decreased IgM level
- no detectable IgM found in serum

spleen hypoplasia
- spleen contains 5 to 9 times fewer nonerythroid cells than wild-type or heterozygous controls

thymus hypoplasia
- thymus contains 15 to 300 times fewer cells than wild-type or heterozygous controls

hematopoietic system phenotype

abnormal B cell differentiation
- spleen and bone marrow lack mature B cells; B cells are IgM and IgD negative, and only 1/4 to 1/3 are B220-positive

abnormal immunoglobulin V(D)J recombination
- absence of V(D)J recombination

abnormal T cell differentiation
- thymocyte development is arrested at an early stage; cells are larger than normal, and are CD3^-, TCR alphabeta-negative, CD8^- CD4^-

abnormal T cell morphology
- no mature T lymphocytes are seen in lymphoid organs
- thymocytes are larger in 4-, 5-, and 7-week old mutants than in controls

abnormal T cell receptor V(D)J recombination
- absence of V(D)J recombination

absent mature B cells
- no mature B lymphocytes are observed in lymphoid organs

decreased IgM level
- no detectable IgM found in serum

spleen hypoplasia
- spleen contains 5 to 9 times fewer nonerythroid cells than wild-type or heterozygous controls

thymus hypoplasia
- thymus contains 15 to 300 times fewer cells than wild-type or heterozygous controls

mammalian phenotype

behavior/neurological phenotype
- Normal - normal activity, coordination and strength; normal nociception

nervous system phenotype
- Normal - brain is normal in structure and size
- brain was normal in structure and size

Genotype: Rag1^tm1Mom/Rag1^tm1Mom
involves: 129S7/SvEvBrd * C57BL/6 * FVB * NOD

endocrine/exocrine gland phenotype

small thymus
- nontransgenic Rag1 homozygotes have extremely small thymi

hematopoietic system phenotype

decreased lymphocyte cell number
- non-transgenic Rag1-null mice display lymphopenia more severe than transgenic Rag1-null mice

small thymus
- nontransgenic Rag1 homozygotes have extremely small thymi

immune system phenotype

decreased lymphocyte cell number
- non-transgenic Rag1-null mice display lymphopenia more severe than transgenic Rag1-null mice

small thymus
- nontransgenic Rag1 homozygotes have extremely small thymi

Genotype: Rag1^tm1Mom/Rag1^tm1Mom
involves: 129S7/SvEvBrd * C57BL/10

mammalian phenotype

skeleton phenotype
- Normal - mice exhibit normal bone morphology

skeleton phenotype

abnormal bone remodeling
- following ovariectamy, mice exhibit an increased bone loss compared to in similarly treated wild-type mice

Genotype: Rag1^tm1Mom/Rag1^tm1Mom
involves: 129S7/SvEvBrd

cellular phenotype

abnormal neuron proliferation
- decrease in hippocampal neurogenesis

nervous system phenotype

abnormal neuron proliferation
- decrease in hippocampal neurogenesis

endocrine/exocrine gland phenotype

abnormal thymus epithelium morphology
- Normal - medullary thymic epithelial cells that present self antigen are present in these mice

hematopoietic system phenotype

abnormal double-negative T cell morphology
- less proportion of these cells are actively cycling compared to controls
- the number of CD44^-HSA⁺CD25^- DN thymyoctes is 2% of controls

abnormal thymus epithelium morphology
- Normal - medullary thymic epithelial cells that present self antigen are present in these mice

immune system phenotype

abnormal double-negative T cell morphology
- less proportion of these cells are actively cycling compared to controls
- the number of CD44^-HSA⁺CD25^- DN thymyoctes is 2% of controls

abnormal thymus epithelium morphology
- Normal - medullary thymic epithelial cells that present self antigen are present in these mice

decreased inflammatory response
- intracolonic administration of the F2r (PAR-1) activating peptide, TFLLR, fails to induce inflammation in mutant colons as in wild-type mice

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

Genotype: Rag1^tm1Mom/Rag1^tm1Mom
involves: 129S7/SvEvBrd * C57BL/6

digestive/alimentary phenotype

decreased susceptibility to induced colitis
- dextran sulfate sodium induced colitis is less severe than in wild-type controls

pigmentation phenotype

abnormal coat/hair pigmentation
- after transplant of CD4-selected splenocytes, mice develop extensive vitiligo

abnormal skin pigmentation
- after transplant of CD4-selected splenocytes, mice develop extensive vitiligo

respiratory system phenotype

abnormal respiratory system morphology
- after 4 weeks, mice show impaired vascular remodeling of the airways in response to Mycoplasma pulmonis infection whereas wild-type show complex growth and reorganization ot the vascular beds

vision/eye phenotype

abnormal eye morphology
- mice develop ocular injury with disruption of retinal architecture after transplant of CD4-selected splenocytes from Tg(Tcra,Tcrb)9Rest/Rag1^--mice

abnormal retina morphology
- mice develop ocular injury with disruption of retinal architecture after transplant of CD4-selected splenocytes from Tg(Tcra,Tcrb)9Rest/Rag1^--mice

hematopoietic system phenotype

decreased neutrophil cell number
- 2 weeks or 1 month after infection with M. pulmonis, neutrophil numbers in the trachea are elevated above uninfected controls but are significantly lower than numbers in trachea of infected wild-type mice

immune system phenotype

abnormal lymphatic vessel morphology
- upon infection with Mycoplasma pulmonis, airway lymphatic vessel remodeling is largely absent from mutants, compared to significant invasion of region by lymphatic vessels in infected wild-type mice

abnormal response to infection
- airway vascular and airway lymphatic vessel remodeling are impaired or absent compared to wild-type mice after M. pulmonis infection

autoimmune response
- antigen-specific autoimmunity developed after CD4-selected splenocytes from Tg(Tcra,Tcrb)9Rest donor mice

decreased neutrophil cell number
- 2 weeks or 1 month after infection with M. pulmonis, neutrophil numbers in the trachea are elevated above uninfected controls but are significantly lower than numbers in trachea of infected wild-type mice

decreased susceptibility to induced colitis
- dextran sulfate sodium induced colitis is less severe than in wild-type controls

integument phenotype

abnormal coat/hair pigmentation
- after transplant of CD4-selected splenocytes, mice develop extensive vitiligo

abnormal skin pigmentation
- after transplant of CD4-selected splenocytes, mice develop extensive vitiligo

References

Mombaerts P; Iacomini J; Johnson RS; Herrup K; Tonegawa S; Papaioannou VE. 1992. RAG-1-deficient mice have no mature B and T lymphocytes. Cell 68(5):869-77PubMed: 1547488 MGI: J:1934

Additional References

Mombaerts P; Clarke AR; Rudnicki MA; Iacomini J; Itohara S; Lafaille JJ; Wang L; Ichikawa Y; Jaenisch R; Hooper ML; Tonegawa S. 1992. Mutations in T-cell antigen receptor genes alpha and beta block thymocyte development at different stages [published erratum appears in Nature 1992 Dec 3;360(6403):491] Nature 360(6401):225-31PubMed: 1359428 MGI: J:3206
Wiekowski MT; Chen SC; Zalamea P; Wilburn BP; Kinsley DJ; Sharif WW; Jensen KK; Hedrick JA; Manfra D; Lira SA. 2001. Disruption of neutrophil migration in a conditional transgenic model: evidence for CXCR2 desensitization in vivo. J Immunol 167(12):7102-10PubMed: 11739532 MGI: J:73096
Petiniot LK; Weaver Z; Vacchio M; Shen R; Wangsa D; Barlow C; Eckhaus M; Steinberg SM; Wynshaw-Boris A; Ried T; Hodes RJ. 2002. RAG-mediated V(D)J recombination is not essential for tumorigenesis in Atm-deficient mice. Mol Cell Biol 22(9):3174-7PubMed: 11940674 MGI: J:75737
Miyamoto A; Nakayama K; Imaki H; Hirose S; Jiang Y; Abe M; Tsukiyama T; Nagahama H; Ohno S; Hatakeyama S; Nakayama KI. 2002. Increased proliferation of B cells and auto-immunity in mice lacking protein kinase Cdelta. Nature 416(6883):865-9PubMed: 11976687 MGI: J:76135
Rathmell JC; Lindsten T; Zong WX; Cinalli RM; Thompson CB. 2002. Deficiency in Bak and Bax perturbs thymic selection and lymphoid homeostasis. Nat Immunol 3(10):932-9PubMed: 12244308 MGI: J:79218
Claudio E; Brown K; Park S; Wang H; Siebenlist U. 2002. BAFF-induced NEMO-independent processing of NF-kappaB2 in maturing B cells. Nat Immunol 3(10):958-65PubMed: 12352969 MGI: J:79239
Seagroves TN; Hadsell D; McManaman J; Palmer C; Liao D; McNulty W; Welm B; Wagner KU; Neville M; Johnson RS. 2003. HIF1alpha is a critical regulator of secretory differentiation and activation, but not vascular expansion, in the mouse mammary gland. Development 130(8):1713-24PubMed: 12620994 MGI: J:82618
Cao Y; Bonizzi G; Seagroves TN; Greten FR; Johnson R; Schmidt EV; Karin M. 2001. IKKalpha provides an essential link between RANK signaling and cyclin D1 expression during mammary gland development. Cell 107(6):763-75PubMed: 11747812 MGI: J:90978

Additional - Rag1^tm1Mom related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Rag1Alternate1
- Genotyping resources and troubleshooting
Breeding Considerations

This Rag1^tm1Mom strain is maintained by mating homozygous siblings. This strain should be housed under pathogen free conditions similar to Prkdc^scid/Prkdc^scid mice or any other immunodeficient strain. Only homozygous mice may be ordered. Expected coat color from breeding:White Bellied Agouti
- Additional Breeding and Husbandry Support
Appearance
- white-bellied agouti
  Related Genotype: A^w/A^w
Citation
When using the RAG-1^- mouse strain in a publication, please cite the originating article(s) and include JAX stock #002096 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 or Homozygous for Rag1<tm1Mom>, 1 pair minimum

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.

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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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Also Known As:RAG-1-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Control Suggestions

Approximate Controls

Additional Information

Selected References

Rag1tm1Mom

Allele Symbol: Rag1tm1Mom

Disease Terms

Research Areas By Phenotype

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

Genotype: Rag1tm1Mom related

Mammalian Phenotype Terms by Genotype

Genotype: Rag1tm1Mom/Rag1tm1Mominvolves: 129S7/SvEvBrd * CD-1

endocrine/exocrine gland phenotype

immune system phenotype

hematopoietic system phenotype

mammalian phenotype

Genotype: Rag1tm1Mom/Rag1tm1Mominvolves: 129S7/SvEvBrd * C57BL/6 * FVB * NOD

endocrine/exocrine gland phenotype

hematopoietic system phenotype

immune system phenotype

Genotype: Rag1tm1Mom/Rag1tm1Mominvolves: 129S7/SvEvBrd * C57BL/10

mammalian phenotype

skeleton phenotype

Genotype: Rag1tm1Mom/Rag1tm1Mominvolves: 129S7/SvEvBrd

cellular phenotype

nervous system phenotype

endocrine/exocrine gland phenotype

hematopoietic system phenotype

immune system phenotype

Genotype: Rag1tm1Mom/Rag1tm1Mominvolves: 129S7/SvEvBrd * C57BL/6

digestive/alimentary phenotype

pigmentation phenotype

respiratory system phenotype

vision/eye phenotype

hematopoietic system phenotype

immune system phenotype

integument phenotype

References

Additional References

Additional - Rag1tm1Mom related

Genotyping Protocols

Breeding Considerations

Appearance

Citation

Animal Health Reports

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

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

Also Known As:RAG-1^-

Rag1^tm1Mom

Allele Symbol: Rag1^tm1Mom

Genotype: Rag1^tm1Mom related

Genotype: Rag1^tm1Mom/Rag1^tm1Mom
involves: 129S7/SvEvBrd * CD-1

Genotype: Rag1^tm1Mom/Rag1^tm1Mom
involves: 129S7/SvEvBrd * C57BL/6 * FVB * NOD

Genotype: Rag1^tm1Mom/Rag1^tm1Mom
involves: 129S7/SvEvBrd * C57BL/10

Genotype: Rag1^tm1Mom/Rag1^tm1Mom
involves: 129S7/SvEvBrd

Genotype: Rag1^tm1Mom/Rag1^tm1Mom
involves: 129S7/SvEvBrd * C57BL/6

Additional - Rag1^tm1Mom related