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Rag2 Targeted Mutation Mice from Taconic Rag2 Targeted Mutation Mice from Taconic In vivo Immunology Model for Drug Discovery and Toxicology The Taconic Rag2 Targeted Mutation Mouse Scientific Profile of the Rag2 Targeted Mutation Mouse1, 2 • Lacks mature T and B lymphocytes due to The Taconic Rag2 Targeted Mutation Mice an inability to initiate V(D)J rearrang-ement. carry a germline mutation in which a large Otherwise, the mouse exhibits apparently portion of the Rag2 coding region is deleted. normal hematopoiesis. Mice homozygous for the mutation are observed Potential Applications of the Rag2 to lack mature T and B lymphocytes. Analysis Targeted Mutation Mouse of these mice indicate that the Rag2 defect blocks T cell and B cell differentiation earlier • Evaluate function of lymphocyte specific and/or more completely than the scid defect. genes in immune cell differentiation (Figure 1). • Reconstitute with human hematopoietic Homozygous mutant mice were found to appear cells for research in AIDS and other immune normal except for immunological defects. cell disorders. Spleens, thymuses, and lymph nodes were small • Model human hematopoiesis for studying and hypoplastic. No detectable alterations were experimental therapeutics or developing observed in other tissues tested. vaccines. • Research the immune system's effect on Mice heterozygous for the mutation were found tumorigenesis and metastasis. to be normal compared with their wild type • Investigate somatic cell therapy in vivo. littermates. • Explore the genetics of autoimmmune or infectious diseases. Figure 1: RAG2 deficient blastocyst complementation assay. Chen, J., Lansford, R., Stewart, V., Young, F., Alt, F. Proceedings of the National Academy of Science 90, 4528-4532. 1993. (Diagram courtesy of Dr. Chen and Dr. Alt.) Taconic Rag2 Mice Background Strains Taconic Model # Nomenclature Background Strain Inbred/ Haplotype Congenic RAG2-M 129S6/SvEvTac-Rag2tm1Fwa 129/SvEv Inbred b 461-M B6.SJL(129S6)- Ptprca/BoCrTac-Rag2tm1Fwa N10 B6.SJL(129S6) Congenic b 601-M C.129S6(B6)-Rag2tm1Fwa N12 C.129S6(B6) Congenic d RAGN12-M B6.129S6-Rag2tm1Fwa N12 B6.129S6 Congenic b Genetic Background Ready for Your Experiments The Taconic Rag2 line is maintained on several Taconic's quality program assures that each different genetic backgrounds to meet your Rag2 Targeted Mutation Mouse is bred for particular research needs (see table). The Rag2 homozygosity. Taconic mice are shipped in mutant mouse on the 129/SvEv background is Taconic Transport Cages (TTCTM) and come on the inbred strain used to create the with an up-to-date health report documenting embryonic stem cells for the initial gene their Murine Pathogen Free (MPFTM) health targeting experiments done in the laboratory of status. Barrier housing conditions are Dr. Fred Alt. The Rag2 Targeted Mutation recommended for maintenance of Rag2 Mouse on the congenic B6.SJL(129S6) homozygous mice. background makes this line useful for their identification in immunological adoptive Related Mouse Models transfer experiments. It is similar to a C57BL/6 background except Pfp/Rag2 (model 001177) - This double that it carries the ptprca and the pep 3b genes targeted mutation exhibits a severe depletion of from the SJL strain of mice. This marker is also NK cell function through the disruption of the sometimes referred to as Ly5.1.3,4 Pfp gene and lacks mature T or B lymphocytes through disruption of the Rag2 gene. It can be The Rag2 mouse is also available on C57BL/6 used to study overall regulation of the immune and BALB/c congenic backgrounds. (See above system or specific areas such as NK or CTL table for haplotypes.) activity, immune suppression and transplantation. This mouse is homozygous for Origin of Models both the disrupted Pfp gene and Rag2 gene. It is an alternative to traditional models bearing The Rag2 mouse was developed in the combinations of naturally occurring mutant laboratory of Frederick W. Alt at Columbia genes such as the scid-bg (Prkdcscid-Foxn1nu) University. The model was created by targeting and bg-nu-xid (Lystbg-Foxn1nu-Btk-xid). the Rag2 gene in CCE ES cells and injecting the targeted cells into blastocysts. Ellis Reinherz of Rag2-HY (model 004079) - The Rag2 gene in the Dana Farber Cancer Institute received Rag2 this model has been inactivated by homologous mice from the Alt lab on a mixed background. recombination therefore no V(D)J The mice were then backcrossed by S. Koyasu rearrangements can occur. The result of this a for 10 generations (N10) to B6.SJL-Ptprc manipulation allows no maturing endogenous T (from Cancer Research). Taconic received stock or B cells. This provides a background to in 1996. The mice were derived by embryo examine the phenotypic expression of the transfer, and the colony is maintained by mating antigen HY transgene. This transgene results in homozygous mice. a large fraction of T-cells expressing an a b -2- TCR specific for a minor histocompatibility For more information or to place an order contact: antigen (H-Y) which is present on male but not TACONIC female cells in the context of MHC Class I (H- One Hudson City Centre b d Hudson, NY 12534 2D ). These mice carry an H2 haplotype which Toll Free: 1-888-TACONIC is a non-selecting background for conventional Phone: 518-537-6208 Fax: 518-537-7287 T-cells. Therefore on a B10.D2 e-mail: [email protected] d background(H2 ), thymocyte development is Internet: http://www.taconic.com arrested at the double positive stage in both in Europe: Taconic Europe male and female Rag2/HY mice. These mice can Bomholtvej 10 P.O. Box 39 DK 8680 Ry DENMARK be useful for studying mechanisms of self- Phone: +45 70 23 04 05 tolerance and lineage commitment and the role Fax: +45 86 84 16 99 e-mail: [email protected] of CD4 and CD 8 molecules in the deletion Internet: http://www.taconic.com process of autospecific cells. References Cited: 1. Shinkai, Y., Rathbun, G., Lam, K. P., Oltz, E. M., Stewart, V., in Japan: CLEA Japan, Inc. Mendelsohn, M., Charron, J., Datta, M., Young, F., Stall, A. M., Phone: 03-5704-7063 and Alt, F. W. Cell 68, 855-867 (1992). Fax: 03-3792-5298 2. Chen, J., Lansford, R., Stewart, V., Young, F., Alt, F. W. e-mail: [email protected] Proceedings of the National Academy of Sciences 90, 4528-4532 Internet: http://clea-japan.com (1993). Rev. 03/08 3. Schulz, R.J., Parkes, A., Mizoguchi, F., Bhan, A.K. and Loyasu, S.(1996) Development of CD4-CD8-αβTCR+NK1.1+ lymphocytes: thymic selection by self antigen. J. Immunol. 157.4379-4389. 4. Komuro, Immunogenetics 1:452, 1975 © Copyright 2008. Taconic Farms, Inc. RG290495 Every Taconic Transgenic Model™ carries a label license granting you a license under Taconic’s in-licensed patent right(s) to use the model in your research. TTM™s are produced and distributed under rights to patents that Taconic has licensed from various institutions, including exclusive distribution rights to Positive Negative Selection and Isogenic DNA gene targeting technologies. Taconic is the only commercial breeder that can supply transgenic models with these licenses for use in your research. Conditions of Use for Taconic Transgenic Models™ TACONIC TRANSGENIC MODELS™ (“MODELS”) are produced and distributed under rights to patents and intellectual property licensed from various institutions. Taconic grants to each purchaser a right under Taconic’s rights in such licensed patents and intellectual property to use the purchased MODEL in consideration of purchasers’ acknowledgement of and agreement to the Terms and Conditions of Sale and the following terms of use: Title to these MODELS and biological materials derived from them remains WITH TACONIC FARMS, INC. The MODELS will be used for research purposes only. The MODELS will not be bred except to obtain embryos or fetuses required for research purposes. The MODELS and biological materials derived from them will not be distributed to third parties or used for commercial purposes. -3- Taconic Transgenic Models Publication Reference List Rag2 Targeted Mutation Mice Acuff, H.B., Carter, K.J., Fingleton, B., Gorden, D.L., Dependent in a Coronavirus Model of Multiple Sclerosis. Matrisian, L.M. (2006) MMP9 from bone marrow-derived American Journal of Pathology, Vol. 164, No. 2, pp. 363-369. cells contributes to survival but not growth of tumor cells in the lung microenvironment. Cancer Research, Vol. 66, No. 1, Daugherty, A., Pure, E., Delfel-Butteiger, D., Chen, S., pp. 259-266. Leferovich, J., Roselaar, S.E., Rader, D.J. (1997) The Effects of Total Lymphocyte Deficiency on the Extent of Amagai, M., Tsunoda, K., Suzuki, H., Nishifuji, K., Koyasu, S., Atherosclerosis in Apolipoprotein E-1- Mice, Journal of Nishikawa, T. (2000) Use of Autoantigen-Knockout Mice in Clinical Investigation, Vol. 100, No. 6, pp. 1575-1580. Developing an Active Autoimmune Disease Model for Pemphigus, Journal of clinical Investigation, Vol. 105, No. 5, Erdman, S.E., Poutahidis, T., Tomczak, M., Rogers, A.B., pp. 625-631. Cormier, K., Plank, B., Horwitz, B.H., Fox, J.G. (2003) CD4+ CD25+ Regulatory T Lymphocytes Inhibit Microbially Aya, K., Alhawagri, M., Hagen-Stapleton, A., Kitaura, H., Induced Colon Cancer in Rag2-Deficient Mice. American Kanagawa, O., Novack, D.V. (2005) NF-κB–inducing kinase Journal of Pathology, Vol. 162, No. 2, pp. 691–702. controls lymphocyte and osteoclast activities in inflammatory arthritis. Journal of Clinical Investigation, Vol. Erlebacher, A., Lukens, A.K., Glimcher, L.H. (2002) Intrinsic 115, No.7, pp. 1848-1854. susceptibility of mouse trophoblasts to natural killer cell- mediated attack in vivo. Proceedings of the National Academy Borsig L, Wong R, Hynes RO, Varki NM, Varki A. (2002) of Science, Vol. 99, No. 26, pp. 16940-16945. Synergistic effects of L- and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate Erlebacher, A., Vencato, D., Price, K.A., Zhang, D., Glimcher, leukocytes as enhancers of metastasis; Proc Natl Acad Sci, L.H.
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