JAX Mouse Strain Datasheet - 003729

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

Stock No:: 003729 |; Rag1 KO

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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
NOD/LtSz	N10+N2F12 (27-MAR-17)

Rag1^tm1Mom

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

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Research Applications

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

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Base Price

Starting at:

$224.00 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. In: . . 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)	RAG-1-; RAG1^null; Rag-; Rag-1KO; Rag1^-; Rag^1tm1Mom
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/Phenotype

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

Genotype: Rag1^tm1Mom related

Cancer Research
- Toxicology
  - B and T cell deficiency, xenograft/transplant host
Hematological Research
- Immunological Defects
  - B and T cell deficiency
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
Internal/Organ Research
- Lymphoid Tissue Defects
  - B and T cell deficiency
Research Tools
- Cancer Research
  - B and T cell deficiency, xenograft/transplant host
- Toxicology Research
  - xenograft/transplant host

Mammalian Phenotype Terms by Genotype

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

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

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

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

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

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

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. In: . . MGI: 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.. In: . . MGI: J:227975

Additional - Rag1^tm1Mom 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.. In: . . MGI: J:202219
Abramson J; Giraud M; Benoist C; Mathis D. 2010. Aire's partners in the molecular control of immunological tolerance.. In: . . MGI: 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.. In: . . MGI: 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.. In: . . MGI: 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.. In: . . MGI: 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.. In: . . MGI: 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.. In: . . MGI: 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.. In: . . MGI: J:174292
Alli R; Nguyen P; Boyd K; Sundberg JP; Geiger TL. 2012. A mouse model of clonal CD8+ T lymphocyte-mediated alopecia areata progressing to alopecia universalis.. In: . . MGI: J:180590
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.. In: . . MGI: 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.. In: . . MGI: J:125443
Alugupalli KR; Leong JM; Woodland RT; Muramatsu M; Honjo T; Gerstein RM. 2004. B1b lymphocytes confer T cell-independent long-lasting immunity.. In: . . MGI: J:93752
Alves NL; Huntington ND; Mention JJ; Richard-Le Goff O; Di Santo JP. 2010. Cutting Edge: a thymocyte-thymic epithelial cell cross-talk dynamically regulates intrathymic IL-7 expression in vivo.. In: . . MGI: J:161220
Amante FH; Haque A; Stanley AC; Rivera Fde L; Randall LM; Wilson YA; Yeo G; Pieper C; Crabb BS; de Koning-Ward TF; Lundie RJ; Good MF; Pinzon-Charry A; Pearson MS; Duke MG; McManus DP; Loukas A; Hill GR; Engwerda CR. 2010. Immune-Mediated Mechanisms of Parasite Tissue Sequestration during Experimental Cerebral Malaria.. In: . . MGI: J:163540
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Arsov I; Adebayo A; Kucerova-Levisohn M; Haye J; MacNeil M; Papavasiliou FN; Yue Z; Ortiz BD. 2011. A role for autophagic protein Beclin 1 early in lymphocyte development.. In: . . MGI: J:169157
Ashbaugh JJ; Brambilla R; Karmally SA; Cabello C; Malek TR; Bethea JR. 2013. IL7Ralpha Contributes to Experimental Autoimmune Encephalomyelitis through Altered T Cell Responses and Nonhematopoietic Cell Lineages.. In: . . MGI: J:195519
Assarsson E; Chambers BJ; Hogstrand K; Berntman E; Lundmark C; Fedorova L; Imreh S; Grandien A; Cardell S; Rozell B; Ljunggren HG. 2007. Severe defect in thymic development in an insertional mutant mouse model.. In: . . MGI: J:145284
Auger JL; Haasken S; Steinert EM; Binstadt BA. 2012. Incomplete TCR-beta allelic exclusion accelerates spontaneous autoimmune arthritis in K/BxN TCR transgenic mice.. In: . . MGI: J:187944
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Bagley AF; Scherz-Shouval R; Galie PA; Zhang AQ; Wyckoff J; Whitesell L; Chen CS; Lindquist S; Bhatia SN. 2015. Endothelial Thermotolerance Impairs Nanoparticle Transport in Tumors.. In: . . MGI: J:225593
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Bankoti R; Gupta K; Levchenko A; Stager S. 2012. Marginal zone B cells regulate antigen-specific T cell responses during infection.. In: . . MGI: J:184071
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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.. In: . . MGI: J:181327
Bassetti MF; White J; Kappler JW; Marrack P. 2009. Transgenic Bcl-3 slows T cell proliferation.. In: . . MGI: 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.. In: . . MGI: 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.. In: . . MGI: 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.. In: . . MGI: J:146118
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Beilke JN; Kuhl NR; Van Kaer L; Gill RG. 2005. NK cells promote islet allograft tolerance via a perforin-dependent mechanism.. In: . . MGI: 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.. In: . . MGI: 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.. In: . . MGI: J:197555
Benahmed F; Chyou S; Dasoveanu D; Chen J; Kumar V; Iwakura Y; Lu TT. 2014. Multiple CD11c+ cells collaboratively express IL-1beta to modulate stromal vascular endothelial growth factor and lymph node vascular-stromal growth.. In: . . MGI: J:209986
Bendix I; Pfueller CF; Leuenberger T; Glezeva N; Siffrin V; Muller Y; Prozorovski T; Hansen W; Topphoff US; Loddenkemper C; Zipp F; Waiczies S. 2010. MAPK3 deficiency drives autoimmunity via DC arming.. In: . . MGI: J:160957
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.. In: . . MGI: J:164685
Bergstrom KS; Guttman JA; Rumi M; Ma C; Bouzari S; Khan MA; Gibson DL; Vogl AW; Vallance BA. 2008. Modulation of intestinal goblet cell function during infection by an attaching and effacing bacterial pathogen.. In: . . MGI: J:130255
Bessler M; Rosti V; Peng Y; Cattoretti G; Notaro R; Ohsako S; Elkon KB; Luzzatto L. 2002. Glycosylphosphatidylinositol-linked proteins are required for maintenance of a normal peripheral lymphoid compartment but not for lymphocyte development.. In: . . MGI: J:78996
Bettelli E; Pagany M; Weiner HL; Linington C; Sobel RA; Kuchroo VK. 2003. Myelin oligodendrocyte glycoprotein-specific T cell receptor transgenic mice develop spontaneous autoimmune optic neuritis.. In: . . MGI: J:83278
Bettini ML; Pan F; Bettini M; Finkelstein D; Rehg JE; Floess S; Bell BD; Ziegler SF; Huehn J; Pardoll DM; Vignali DA. 2012. Loss of epigenetic modification driven by the Foxp3 transcription factor leads to regulatory T cell insufficiency.. In: . . MGI: J:187320
Binder GK; Griffin DE. 2001. Interferon-gamma-mediated site-specific clearance of alphavirus from CNS neurons.. In: . . MGI: 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.. In: . . MGI: J:153217
Bizargity P; Del Rio R; Phillippe M; Teuscher C; Bonney EA. 2009. Resistance to lipopolysaccharide-induced preterm delivery mediated by regulatory T cell function in mice.. In: . . MGI: J:149636
Blache CA; Manuel ER; Kaltcheva TI; Wong AN; Ellenhorn JD; Blazar BR; Diamond DJ. 2012. Systemic delivery of Salmonella typhimurium transformed with IDO shRNA enhances intratumoral vector colonization and suppresses tumor growth.. In: . . MGI: J:193636
Blanc L; Ciciotte SL; Gwynn B; Hildick-Smith GJ; Pierce EL; Soltis KA; Cooney JD; Paw BH; Peters LL. 2012. Critical function for the Ras-GTPase activating protein RASA3 in vertebrate erythropoiesis and megakaryopoiesis.. In: . . MGI: J:186485
Block MS; Mendez-Fernandez YV; Van Keulen VP; Hansen MJ; Allen KS; Taboas AL; Rodriguez M; Pease LR. 2005. Inability of bm14 mice to respond to Theiler's murine encephalomyelitis virus is caused by defective antigen presentation, not repertoire selection.. In: . . MGI: J:97717
Bonnet MC; Preukschat D; Welz PS; van Loo G; Ermolaeva MA; Bloch W; Haase I; Pasparakis M. 2011. The Adaptor Protein FADD Protects Epidermal Keratinocytes from Necroptosis In Vivo and Prevents Skin Inflammation.. In: . . MGI: J:177639
Borghesi L; Hsu LY; Miller JP; Anderson M; Herzenberg L; Herzenberg L; Schlissel MS; Allman D; Gerstein RM. 2004. B lineage-specific regulation of V(D)J recombinase activity is established in common lymphoid progenitors.. In: . . MGI: J:119401
Botelho FM; Gaschler GJ; Kianpour S; Zavitz CC; Trimble NJ; Nikota JK; Bauer CM; Stampfli MR. 2010. Innate immune processes are sufficient for driving cigarette smoke-induced inflammation in mice.. In: . . MGI: J:171489
Bouchery T; Kyle R; Camberis M; Shepherd A; Filbey K; Smith A; Harvie M; Painter G; Johnston K; Ferguson P; Jain R; Roediger B; Delahunt B; Weninger W; Forbes-Blom E; Le Gros G. 2015. ILC2s and T cells cooperate to ensure maintenance of M2 macrophages for lung immunity against hookworms.. In: . . MGI: J:226375
Bour-Jordan H; Salomon BL; Thompson HL; Szot GL; Bernhard MR; Bluestone JA. 2004. Costimulation controls diabetes by altering the balance of pathogenic and regulatory T cells.. In: . . MGI: J:93421
Bournazos S; Klein F; Pietzsch J; Seaman MS; Nussenzweig MC; Ravetch JV. 2014. Broadly neutralizing anti-HIV-1 antibodies require Fc effector functions for in vivo activity.. In: . . MGI: J:214949
Brady BL; Bassing CH. 2011. Differential regulation of proximal and distal Vbeta segments upstream of a functional VDJbeta1 rearrangement upon beta-selection.. In: . . MGI: J:179246
Brady BL; Rupp LJ; Bassing CH. 2013. Requirement for dicer in survival of proliferating thymocytes experiencing DNA double-strand breaks.. In: . . MGI: J:194523
Brehm MA; Racki WJ; Leif J; Burzenski L; Hosur V; Wetmore A; Gott B; Herlihy M; Ignotz R; Dunn R; Shultz LD; Greiner DL. 2012. Engraftment of human HSC in non-irradiated newborn NOD-scid IL2rgammanull mice is enhanced by transgenic expression of membrane-bound human SCF.. In: . . MGI: J:180273
Brickshawana A; Shapiro VS; Kita H; Pease LR. 2011. Lineage(-)Sca1+c-Kit(-)CD25+ cells are IL-33-responsive type 2 innate cells in the mouse bone marrow.. In: . . MGI: J:179700
Brien JD; Daffis S; Lazear HM; Cho H; Suthar MS; Gale M Jr; Diamond MS. 2011. Interferon regulatory factor-1 (IRF-1) shapes both innate and CD8(+) T cell immune responses against West Nile virus infection.. In: . . MGI: J:183131
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Also Known As: Rag1 KO

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Rag1tm1Mom

Allele Symbol: Rag1tm1Mom

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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)-Rag1tm1Mom

immune system phenotype

hematopoietic system phenotype

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Additional - Rag1tm1Mom related

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Rag1^tm1Mom

Allele Symbol: Rag1^tm1Mom

Genotype: Rag1^tm1Mom related

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

Additional - Rag1^tm1Mom related