JAX
Mouse Strain Datasheet - 003729
NOD.129S7(B6)-Rag1tm1Mom/J
Also Known As: Rag1 KO
Mice homozygous for Rag1tm1Mom 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 |
|---|---|
|
NOD/LtSz |
N10+N2F12
|
Rag1tm1Mom
| Allele Type | Gene Symbol | Gene Name |
|---|---|---|
| Targeted (Null/Knockout) | Rag1 | recombination activating gene 1 |
Research Applications
- Diabetes and Obesity Research
- Research Tools
- Cancer Research
- Hematological Research
- Immunology, Inflammation and Autoimmunity Research
- Internal/Organ Research
Detailed Description
Mice homozygous for the Rag1tm1Mom mutation produce no mature T cells or B cells. Their phenotype can be described as a "non-leaky" severe combined immune deficiency. (Prkdcscid/Prkdcscid) mice produce some B cells and IgM. NOD.129S7(B6)-Rag1tm1Mom/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-Prkdcscid/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 Rag1tm1Mom 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
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):2496-507. PubMed: 10679087MGI: J:60800
Rag1tm1Mom
Allele Symbol: Rag1tm1Mom
| Allele Name | targeted mutation 1, Peter Mombaerts |
|---|---|
| Allele Type | Targeted (Null/Knockout) |
| Allele Synonym(s) | RAG-1-; RAG1null; Rag-; Rag-1KO; Rag1-; Rag1tm1Mom |
| Gene Symbol and Name | Rag1, recombination activating gene 1 |
| Gene Synonym(s) | RAG-1; RNF74; Rag-1; 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 Terms
Research Areas By Genotype
This mouse can be used to support research in many areas including:
- Diabetes and Obesity Research
- Islet Transplantation Studies
- Type 1 Diabetes (IDDM) Analysis Strains
- NOD Congenics with Mutations Affecting Immunocompetence
- Research Tools
- Immunology, Inflammation and Autoimmunity Research
- B and T cell deficiency
- Immunology, Inflammation and Autoimmunity Research
Genotype: Rag1tm1Mom related
- Cancer Research
- Toxicology
- B and T cell deficiency, xenograft/transplant host
- Toxicology
- Hematological Research
- Immunological Defects
- B and T cell deficiency
- Immunological Defects
- Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
- B and T cell deficiency
- Inflammation
- B and T cell deficiency
- T Cell Receptor Signaling Defects
- B and T cell deficiency
- Immunodeficiency
- Internal/Organ Research
- Lymphoid Tissue Defects
- B and T cell deficiency
- Lymphoid Tissue Defects
- Research Tools
- Cancer Research
- B and T cell deficiency, xenograft/transplant host
- Toxicology Research
- xenograft/transplant host
- Cancer Research
Mammalian Phenotype Terms by Genotype
Genotype: Rag1tm1Mom/Rag1tm1Mom
NOD.129S7(B6)-Rag1tm1Mom
immune system phenotype
- abnormal level of surface class II molecules
- four to five-fold decrease in cells expressing I-Ag7 as compared to NOD control (MGI Ref ID J:109843)
- decreased CD4-positive, alpha beta T cell number
- spleens of 8-11 week old mice are deficient in CD3+ CD4+ T cells (MGI Ref ID J:109843)
- decreased CD8-positive, alpha-beta T cell number
- spleens of 8-11 week old mice are deficient in CD3+ CD8+ T cells (MGI Ref ID J:109843)
- decreased immunoglobulin level
- no serum immunoglobulin is detected in 218-334 day old mice (MGI Ref ID J:109843)
- decreased mature B cell number
- spleens of 8-11 week old mice are deficient in Igkappa+ B220+ T cells (MGI Ref ID J:109843)
- 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 (MGI Ref ID J:109843)
- increased NK cell number
- numbers of NK cells are increased in comparison to NOD controls (MGI Ref ID J:109843)
- increased granulocyte number
- numbers of granulocytes are increased in comparison to NOD controls (MGI Ref ID J:109843)
- increased immature B cell number
- IgLkappa- B220+ immature B cell numbers are increased as compared to NOD controls (MGI Ref ID J:109843)
- increased macrophage cell number
- numbers of macrophages are increased in comparison to NOD controls (MGI Ref ID J:109843)
- spleen hypoplasia
- nucleated spleen cells are reduced in 8-11 week old mice as compared to NOD control (MGI Ref ID J:109843)
hematopoietic system phenotype
- abnormal level of surface class II molecules
- four to five-fold decrease in cells expressing I-Ag7 as compared to NOD control (MGI Ref ID J:109843)
- decreased CD4-positive, alpha beta T cell number
- spleens of 8-11 week old mice are deficient in CD3+ CD4+ T cells (MGI Ref ID J:109843)
- decreased CD8-positive, alpha-beta T cell number
- spleens of 8-11 week old mice are deficient in CD3+ CD8+ T cells (MGI Ref ID J:109843)
- decreased immunoglobulin level
- no serum immunoglobulin is detected in 218-334 day old mice (MGI Ref ID J:109843)
- decreased mature B cell number
- spleens of 8-11 week old mice are deficient in Igkappa+ B220+ T cells (MGI Ref ID J:109843)
- 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 (MGI Ref ID J:109843)
- increased NK cell number
- numbers of NK cells are increased in comparison to NOD controls (MGI Ref ID J:109843)
- increased granulocyte number
- numbers of granulocytes are increased in comparison to NOD controls (MGI Ref ID J:109843)
- increased immature B cell number
- IgLkappa- B220+ immature B cell numbers are increased as compared to NOD controls (MGI Ref ID J:109843)
- increased macrophage cell number
- numbers of macrophages are increased in comparison to NOD controls (MGI Ref ID J:109843)
- spleen hypoplasia
- nucleated spleen cells are reduced in 8-11 week old mice as compared to NOD control (MGI Ref ID J:109843)
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):2496-507. PubMed: 10679087MGI: J:60800
Additional References
- 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):1169-79. PubMed: 24798995MGI: J:227975
Additional - Rag1tm1Mom related
- Abe K; Wechs S; Kalaydjiev S; Franz TJ; Busch DH; Fuchs H; Soewarto D; Behrendt H; Wagner S; Jakob T; Hrabe de Angelis M. 2008. Novel lymphocyte-independent mechanisms to initiate inflammatory arthritis via bone marrow-derived cells of Ali18 mutant mice. Rheumatology (Oxford) 47(3):292-300. PubMed: 18276736MGI: J:202219
- Abramson J; Giraud M; Benoist C; Mathis D. 2010. Aire's partners in the molecular control of immunological tolerance. Cell 140(1):123-35. PubMed: 20085707MGI: J:158990
- Achuthan A; Cook AD; Lee MC; Saleh R; Khiew HW; Chang MW; Louis C; Fleetwood AJ; Lacey DC; Christensen AD; Frye AT; Lam PY; Kusano H; Nomura K; Steiner N; Forster I; Nutt SL; Olshansky M; Turner SJ; Hamilton JA. 2016. Granulocyte macrophage colony-stimulating factor induces CCL17 production via IRF4 to mediate inflammation. J Clin Invest 126(9):3453-66. PubMed: 27525438MGI: J:237243
- Afshar-Sterle S; Zotos D; Bernard NJ; Scherger AK; Rodling L; Alsop AE; Walker J; Masson F; Belz GT; Corcoran LM; O'Reilly LA; Strasser A; Smyth MJ; Johnstone R; Tarlinton DM; Nutt SL; Kallies A. 2014. Fas ligand-mediated immune surveillance by T cells is essential for the control of spontaneous B cell lymphomas. Nat Med 20(3):283-90. PubMed: 24487434MGI: J:208773
- Ahern PP; Schiering C; Buonocore S; McGeachy MJ; Cua DJ; Maloy KJ; Powrie F. 2010. Interleukin-23 drives intestinal inflammation through direct activity on T cells. Immunity 33(2):279-88. PubMed: 20732640MGI: J:163906
- Ahn S; Lee G; Yang SJ; Lee D; Lee S; Shin HS; Kim MC; Lee KN; Palmer DC; Theoret MR; Jenkinson EJ; Anderson G; Restifo NP; Kim MG. 2008. TSCOT+ thymic epithelial cell-mediated sensitive CD4 tolerance by direct presentation. PLoS Biol 6(8):e191. PubMed: 18684012MGI: J:140121
- Ait-Azzouzene D; Verkoczy L; Peters J; Gavin A; Skog P; Vela JL; Nemazee D. 2005. An immunoglobulin C{kappa}-reactive single chain antibody fusion protein induces tolerance through receptor editing in a normal polyclonal immune system. J Exp Med 201(5):817-28. PubMed: 15738053MGI: J:96759
- Akkina R; Berges BK; Palmer BE; Remling L; Neff CP; Kuruvilla J; Connick E; Folkvord J; Gagliardi K; Kassu A; Akkina SR. 2011. Humanized Rag1gammac Mice Support Multilineage Hematopoiesis and Are Susceptible to HIV-1 Infection via Systemic and Vaginal Routes. PLoS One 6(6):e20169. PubMed: 21695116MGI: J:174292
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- Almeida AR; Arroz-Madeira S; Fonseca-Pereira D; Ribeiro H; Lasrado R; Pachnis V; Veiga-Fernandes H. 2012. RET/GFRalpha signals are dispensable for thymic T cell development in vivo. PLoS One 7(12):e52949. PubMed: 23300832MGI: J:195828
- Alugupalli KR; Gerstein RM; Chen J; Szomolanyi-Tsuda E; Woodland RT; Leong JM. 2003. The resolution of relapsing fever borreliosis requires IgM and is concurrent with expansion of B1b lymphocytes. J Immunol 170(7):3819-27. PubMed: 12646649MGI: J:125443
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- Bartemes KR; Iijima K; Kobayashi T; Kephart GM; McKenzie AN; Kita H. 2012. IL-33-responsive lineage- CD25+ CD44(hi) lymphoid cells mediate innate type 2 immunity and allergic inflammation in the lungs. J Immunol 188(3):1503-13. PubMed: 22198948MGI: J:180763
- Basha G; Omilusik K; Chavez-Steenbock A; Reinicke AT; Lack N; Choi KB; Jefferies WA. 2012. A CD74-dependent MHC class I endolysosomal cross-presentation pathway. Nat Immunol 13(3):237-245. PubMed: 22306692MGI: J:181327
- Bassetti MF; White J; Kappler JW; Marrack P. 2009. Transgenic Bcl-3 slows T cell proliferation. Int Immunol 21(4):339-48. PubMed: 19208752MGI: J:147105
- Beal AM; Ramos-Hernandez N; Riling CR; Nowelsky EA; Oliver PM. 2011. TGF-beta induces the expression of the adaptor Ndfip1 to silence IL-4 production during iT(reg) cell differentiation. Nat Immunol 13(1):77-85. PubMed: 22080920MGI: J:179003
- Beamer CA; Migliaccio CT; Jessop F; Trapkus M; Yuan D; Holian A. 2010. Innate immune processes are sufficient for driving silicosis in mice. J Leukoc Biol 88(3):547-57. PubMed: 20576854MGI: J:164920
- Behrens EM; Sriram U; Shivers DK; Gallucci M; Ma Z; Finkel TH; Gallucci S. 2007. Complement receptor 3 ligation of dendritic cells suppresses their stimulatory capacity. J Immunol 178(10):6268-79. PubMed: 17475855MGI: J:146118
- Beier UH; Angelin A; Akimova T; Wang L; Liu Y; Xiao H; Koike MA; Hancock SA; Bhatti TR; Han R; Jiao J; Veasey SC; Sims CA; Baur JA; Wallace DC; Hancock WW. 2015. Essential role of mitochondrial energy metabolism in Foxp3(+) T-regulatory cell function and allograft survival. FASEB J 29(6):2315-26. PubMed: 25681462MGI: J:223218
- Beilke JN; Kuhl NR; Van Kaer L; Gill RG. 2005. NK cells promote islet allograft tolerance via a perforin-dependent mechanism. Nat Med 11(10):1059-65. PubMed: 16155578MGI: J:101693
- Belkaid Y; Von Stebut E; Mendez S; Lira R; Caler E; Bertholet S; Udey MC; Sacks D. 2002. CD8+ T cells are required for primary immunity in C57BL/6 mice following low-dose, intradermal challenge with Leishmania major. J Immunol 168(8):3992-4000. PubMed: 11937556MGI: J:125458
- Ben-Sasson SZ; Hogg A; Hu-Li J; Wingfield P; Chen X; Crank M; Caucheteux S; Ratner-Hurevich M; Berzofsky JA; Nir-Paz R; Paul WE. 2013. IL-1 enhances expansion, effector function, tissue localization, and memory response of antigen-specific CD8 T cells. J Exp Med 210(3):491-502. PubMed: 23460726MGI: J:197555
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- Berger SB; Romero X; Ma C; Wang G; Faubion WA; Liao G; Compeer E; Keszei M; Rameh L; Wang N; Boes M; Regueiro JR; Reinecker HC; Terhorst C. 2010. SLAM is a microbial sensor that regulates bacterial phagosome functions in macrophages. Nat Immunol 11(10):920-7. PubMed: 20818396MGI: J:164685
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- Binder GK; Griffin DE. 2001. Interferon-gamma-mediated site-specific clearance of alphavirus from CNS neurons. Science 293(5528):303-6. PubMed: 11452126MGI: J:125465
- Binstadt BA; Hebert JL; Ortiz-Lopez A; Bronson R; Benoist C; Mathis D. 2009. The same systemic autoimmune disease provokes arthritis and endocarditis via distinct mechanisms. Proc Natl Acad Sci U S A 106(39):16758-63. PubMed: 19805369MGI: J:153217
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