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Immunology and Inflammation Solutions MODELS AND SERVICES DESIGNED TO TAKE YOUR STUDY FURTHER IMMUNOLOGY AND INFLAMMATION TACONIC BIOSCIENCES Immunology and Inflammation Solutions The immune system plays a pivotal role in the pathogenesis of many diseases, including autoimmune, allergic and infectious diseases, cancer, and atherosclerosis. Taconic Biosciences provides models and services to help explore those connections and model human disease. Genetically engineered and immune system engrafted models offer a unique opportunity for advancing immunology and inflammationrelated research. Taconic provides easy access to an exclusive portfolio of models designed to help grow and accelerate our clients’ drug discovery pipeline. In addition to a broad spectrum of mechanistic and disease models in immunology and inflammation, Taconic offers a range of precision research models, including models with human gene replacement or mutation or, cell and tissue engraftment. The use of human immune system engrafted mice has proved to be advantageous in a wide variety of applications including immunomodulatory therapy studies and autoimmune and infectious disease studies. The humanized TNF-α model, which overexpresses human TNF-α and spontaneously develops arthritis, is a superb model for studying biosimilars and new drugs directed at TNF-α. TO ORDER US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Immunology and Inflammation IMMUNOLOGY AND INFLAMMATION TACONIC BIOSCIENCES GERM-FREE MODELS The microbiome has become a major focus of many studies in the realm of immunology, oncology and inflammation. Taconic offers both the C57BL/6NTac inbred mouse and the Swiss Webster outbred mouse as off-the-shelf germ-free options. These rodents are free of all aerobic and anaerobic organisms. Germ-free mice are the starting point for many microbiome studies, as they can be associated with the flora of choice. Taconic also offers custom germ-free derivations and breeding options. SEGMENTED FILAMENTOUS BACTERIA (SFB) There is growing evidence that segmented filamentous bacteria (SFB) can alter the immune system. Knowing whether SFB is present or absent in a model allows the investigator to control for this variable, making results more reproducible. While SFB is only one component of the gut microbiome, for many models the impact could be significant. Taconic includes SFB on all health reports. The Taconic GermFree, Defined Flora and Excluded Flora health designations exclude SFB. DISCUSS YOUR NEEDS US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Immunology and Inflammation IMMUNOLOGY AND INFLAMMATION TACONIC BIOSCIENCES TRADITIONAL MODELS BLACK 6 N OM EN CLATURE INBRED MOUSE C57BL/6NTac • The most widely used inbred as the genetic background for transgenic and mutant mice. • Popular in research applications of oncology, immunology and toxicology. • Now available at the Germ-Free health standard in addition to Excluded Flora, Restricted Flora™ and Murine Pathogen Free™ health profiles. The wide variety of health designations available makes the B6 model ideal for microbiome studies. • B6NTac is an excellent choice for the chronic experimental autoimmune encephalomyelitis model of multiple sclerosis. • Used in ovalbumin induced hypersensitivity. • Applications in infectious disease studies. • May also be used for DSS-induced colitis, induced model of systemic lupus erythematosus (SLE) and CIA-induced arthritis. MODEL NUMBER B6 BALB/c INBRED MOUSE • Often used for the production of monoclonal antibodies using hybridomas of BALB/c spleen cell origin. • Exhibits good breeding performance and long reproductive life span. BALB/c NO MENCL AT U RE • Used in studies of innate and adaptive immunity. BALB/c Bom NO MENCLATUR E BALB/cA Bom N OM EN CLATUR E BALB/cAnNTac BALB/cJBomTac BALB/cABomTac MODEL NUMBER BALB MODEL NUMBER BALJBO MODEL NUMBER BALBOM TO ORDER US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Immunology and Inflammation IMMUNOLOGY AND INFLAMMATION TACONIC BIOSCIENCES DBA/1 N OM ENCLATURE DBA/1JBomTac INBRED MOUSE • Suitable general-purpose research model for immunology and inflammation research. • Widely used as a model of autoimmunity, especially for collageninduced studies of rheumatoid arthritis. • High incidence of mammary tumors. MODEL NUMBER DBA1BO B6.SJL N OM ENCLATURE B6.SJL-Ptprca/BoyAiTac CONGENIC MOUSE • Genetically similar to the C57BL/6Boy strain except that it carries the Ptprca allele (protein-tyrosine phosphatase, receptor type c locus previously known as CD45.1, Ly5.1) and the Pep3b allele from the SJL/J strain. • The unique lymphocyte cell surface antigen produced by Ptprca makes this strain useful for immunological adoptive transfer experiments and useful as a background for GEMs used in adoptive transfer studies. MODEL NUMBER 4007 DISCUSS YOUR NEEDS US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Immunology and Inflammation IMMUNOLOGY AND INFLAMMATION TACONIC BIOSCIENCES SPONTANEOUS MUTANT MODELS NIH nude N OM EN CLATURE NTac:NIH-Foxn1rnu SPONTANEOUS MUTANT RAT T CELL DEFICIENT • Exhibits deficient T cell activity with lymph nodes and Peyers patches showing lymphocyte depletion in T-lymphocyte dependent regions. • In this outbred immunodeficient model, the whiskers are present in the homozygous nude rat, but present as bent with some short hairs on the head and occasionally on the rest of the body (with age some hair growth occurs, but rats become hairless again within a few weeks). • Skin of homozygous rat is generally pigmented, but occasionally an albino rat is seen. • Good xenograft host. • Used in infectious disease studies and as a model of IBS. MODEL NUMBER NIHRNU B6 nude N OM EN CLATURE B6.Cg/NTac-Foxn1nu NE10 SPONTANEOUS MUTANT MOUSE T CELL DEFICIENT • The autosomal recessive nude gene in homozygous (nu/nu) mice causes the lack of fur and an abnormal thymus. Deficiency in T cell function allows athymic mice to accept and grow xenografts as well as allografts of normal and malignant tissues. • Foxn1nu mutation backcrossed to the C57BL/6NTac inbred strain for ten generations. • An appropriate model for adoptive transfer experiments among other strains on the B6 background. • Used to study infectious diseases including HIV and other viral infections. MODEL NUMBER B6NU BALB/c nude N OM EN CLATURE C.Cg/AnNTac-Foxn1nu NE9 SPONTANEOUS MUTANT MOUSE T CELL DEFICIENT • Foxn1nu mutation backcrossed to the BALB/cAnN inbred strain for nine generations. • Available in two health designations: Defined Flora from gnotobiotic isolators and Restricted Flora™ from Isolated Barrier Units™. • Appropriate model for adoptive transfer experiments among other strains on the BALB/c background MODEL NUMBER BALBNU TO ORDER US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Immunology and Inflammation IMMUNOLOGY AND INFLAMMATION TACONIC BIOSCIENCES NCr nude N OM ENCLATURE CrTac:NCr-Foxn1nu SPONTANEOUS MUTANT MOUSE T CELL DEFICIENT • Outbred background originated from an accidental cross between the BALB/c inbred nude and NIH(S) outbred nude mice. • The standard athymic model for National Cancer Institute (NCI) studies as well as many pharmaceutical and institutional oncology screening programs. • Used in autoimmune disease studies and transplantation. MODEL NUMBER NCRNU NMRI nude N OM ENCLATURE BomTac:NMRI-Foxn1nu SPONTANEOUS MUTANT MOUSE T CELL DEFICIENT • Foxn1nu mutation backcrossed to the NMRI outbred stock. • A good general purpose outbred nude. Used in autoimmune disease studies and transplantation. MODEL NUMBER NMRINU C.B-17 scid N OM ENCLATURE C.B-Igh-1b/IcrTac-Prkdcscid SPONTANEOUS MUTANT MOUSE T & B CELL DEFICIENT • Mice homozygous for the Prkdcscid mutation lack both T and B cells due to a defect in V(D)J recombination. Therefore, they easily accept foreign tissue transplants, including human tumors, making them effective models for testing new cancer treatments and as hosts for human immune system tissues (i.e. SCID-hu). • This is the original congenic background strain on which Dr. Mel Bosma discovered the spontaneous scid mutation. • Available at three health designations: Defined Flora from gnotobiotic isolators and Excluded Flora and Restricted Flora™ from Isolated Barrier Units™. • Used in studies of adaptive immunity and infectious disease. MODEL NUMBER CB17SC DISCUSS YOUR NEEDS US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Immunology and Inflammation IMMUNOLOGY AND INFLAMMATION TACONIC BIOSCIENCES ICR scid N OM EN CLATURE IcrTac:ICR-Prkdcscid SPONTANEOUS MUTANT MOUSE T & B CELL DEFICIENT • Equivalent to the C.B-17 scid in severity of immunodeficiency, this outbred background exhibits a significantly reduced incidence of spontaneous Ig production (leakiness). • Gains weight faster than the C.B-17 scid which makes the ICR scid better suited for ascites production from heterohybridomas and as a host for tumor lines. • Mice homozygous for the Prkdcscid mutation lack both T and B cells due to a defect in V(D)J recombination. Therefore, they easily accept foreign tissue transplants, including human tumors, making them effective models for testing new cancer treatments. SCID mice are also useful for examining the relationship between immunity and disease. MODEL NUMBER ICRSC NOD scid N OM EN CLATURE NOD/MrkBomTac-Prkdcscid SPONTANEOUS MUTANT MOUSE T&B CELL DEFICIENT AND REDUCED NK FUNCTION • The scid mutation has been transferred onto a diabetessusceptible Non-Obese Diabetic (NOD) background, making it a great model for metabolic disorder research. Note: The NOD scid does not develop diabetes. • The multiple immunity defects unique to this model provide an excellent system for reconstitution with human hematopoietic cells, making it an exceptional model for HIV-1 research and gene therapy studies. • Short life span of 8-9 months due to lethal thymic lymphomas. • Reduced NK cell activity due to NOD background. • Useful model for cancer research into increased tumor incidence, particularly lymphomas and thymic tumors. MODEL NUMBER NODSC Scid-beige N OM EN CLATURE SPONTANEOUS MUTANT MOUSE T&B CELL DEFICIENT AND REDUCED NK CELLS • The mutations were backcrossed seven generations to the congenic C.B-17 background. • This double mutant model carries the scid mutation which causes a lack of both T and B lymphocytes due to a defect in V(D)J recombination. C.B-Igh-1b/GbmsTac-Prkdcscid-Lystbg N7 • Model also carries the beige mutation which results in cytotoxic T cell and macrophage defects as well as selective impairment of NK cell functions. As a result, scid-beige mice are an improved model for some types of xenotransplants. • The scid-beige strain has a lower incidence of serum Ig relative to the C.B-17 scid strain. MODEL NUMBER CBSCBG TO ORDER US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Immunology and Inflammation IMMUNOLOGY AND INFLAMMATION TACONIC BIOSCIENCES IMMUNOLOGY RANGE COMPARISON TABLE Listed below is information specific to Taconic’s Murine Pathogen FreeTM (MPFTM), Restricted FloraTM (RFTM), Excluded Flora (EF) and Defined Flora (DF) immunodeficient rodents. Taconic currently produces immunodeficient MODEL NUMBER MODEL NAME BALBNU BALB/c nude mouse B6NU B6 nude mouse NCRNU NCr nude mouse NMRINU NMRI nude mouse NIHRNU NIH nude rat 1147 Jh mouse PFPN12° Pfp Knockout (C57BL/6) mouse CB17SC C.B.17 scid mouse ICRSC ICR scid mouse models (both spontaneous and genetically modified mutations) on different background strains (and coat colors) and of differing health/ microbiological profiles. COAT COLOR To inquire about availability of your model of interest at particular health designations, visit Taconic.com/healthstandards CELL DEFICIENCES OTHER IMMUNODEFICIENCIES Severe depletion of NK cell function Defective dendritic cells & macrophages and reduced complement activity. Shows reduced NK function NODSC NOD scid mouse RAG2 Rag2 (129S6) mouse 461° Rag2 (B6.SJL) mouse 601 Rag2 (BALB/c) mouse RAGN12 Rag2 (C57BL/6) mouse CBSCBG Scid-beige mouse 1177° Pfp/Rag2 (C57BL/6) mouse 4111 Rag2/Il2rg Double Knockout Mouse Dysfunctional dendritic cells 11503 CIEA BRG mouse Dysfunctional dendritic cells NOG CIEA NOG mouse® Reduced complement activity, dysfunctional macrophages and dendritic cells, deficiencies in immune signaling, including cytokine production. The most immune deficient mouse available. Severe depletion of NK cell function KE Y: COAT COLOR CELL DEFICIENCIES Black and White Nude Albino Nude Black T Cell Deficient NK Cell Deficient Black Nude White-bellied agouti Albino B Cell Deficient MHC Deficient ° Model is cryopreserved DISCUSS YOUR NEEDS US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Immunology and Inflammation IMMUNOLOGY AND INFLAMMATION TACONIC BIOSCIENCES IMMUNOLOGY RANGE COMPARISON TABLE cont’d MODEL NUMBER MODEL NAME COAT COLOR CELL DEFICIENCES B2MN12 ß2m (C57BL/6) mouse Depletion of CD8+ T cells 4026° Abb (B6.SJL) mouse Depletion of CD8+ T cells 4080° Abb/B2m (C57BL/6) mouse Depletion of CD4+ and CD8+ T cells ABBN12 Abb (C57BL/6) mouse Depletion of CD8+ T cells 1896 Rag2/OT-II mouse Expresses altered T cell population 2334 Rag2/OT-I mouse Expresses altered T cell population OTHER IMMUNODEFICIENCIES K EY: COAT COLOR CELL DEFICIENCIES Black and White Nude Albino Nude Black T Cell Deficient NK Cell Deficient Black Nude White-bellied agouti Albino B Cell Deficient MHC Deficient ° Model is cryopreserved TO ORDER US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Immunology and Inflammation TACONIC BIOSCIENCES IMMUNOLOGY AND INFLAMMATION GEMS GENETICALLY ENGINEERED MODELS To keep up with today’s fast-paced research, Taconic recognizes our customers’ need for speed and accessibility when it comes to genetically engineered models (GEMs) for immunology research. This portfolio provides quick access to advanced research models that are fully licensed and available in typical study quantities. Each GEM carries a license granting our customers the intellectual property rights to use the GEM in their research. Take advantage of Taconic’s GEM portfolio to avoid the challenges and cost of locating, licensing and breeding the models you need. Abb (H2-Ab1) N OM ENCLATURE B6.129-H2-Ab1tm1Gru N12 CONSTITUTIVE KNOCK OUT C57BL/6 BACKGROUND • Contains a disruption of the H2-Ab1 gene. • Useful in transplantation, gene therapy and immunological disease research. • Expresses no A or E MHC class II molecules and therefore lacks most CD4+ T cells. MODEL NUMBER ABBN12 B2m (β2m) N OM EN CLATURE B6.129-B2mtm1Jae N12 CONSTITUTIVE KNOCK OUT C57BL/6 BACKGROUND • Contains a disruption of the beta-2-microglobulin gene. • These MHC class I deficient mice are depleted of CD8+ T cells (lack the NK1.1+ CD4+ T cell population as well). • Useful in transplantation, gene therapy and immunological disease research. MODEL NUMBER B2MN12 DISCUSS YOUR NEEDS US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Immunology and Inflammation IMMUNOLOGY AND INFLAMMATION TACONIC BIOSCIENCES Abb–B2m N OM EN CLATURE B6.129-H2-Ab1tm1Gru B2mtm1Jae N17 CONSTITUTIVE KNOCK OUT C57BL/6 BACKGROUND • This double targeted mutation contains disruption of both H2-Ab1 and B2m genes, combining the characteristics of the two individual targeted mutation models. • Useful in transplantation, gene therapy and immunological disease research. • Cryopreserved. MODEL NUMBER 4080 Ccr2 N OM EN CLATURE B6.129P2-Ccr2tm1Mae N10 CONSTITUTIVE KNOCK OUT C57BL/6 BACKGROUND • Disruption of the Ccr2 gene results in defects in macrophage trafficking • Useful for elucidating the function of cells expressing Ccr2 during immune and inflammatory processes. • Useful for the study of asthma, arthritis and colitis. • Cryopreserved. MODEL NUMBER 3736 Ccr5 N OM EN CLATURE B6.129P2-Ccr5tm1Kuz N10 CONSTITUTIVE KNOCK OUT C57BL/6 BACKGROUND • Disruption of the chemokine receptor 5 (Ccr5) gene results in altered immune responses. • The Ccr5 is the main chemokine receptor for HIV-1 in humans. • Useful in studies of infectious diseases, including HIV-1, malaria, influenza and fungal infections, as well as autoimmune disorders. • Cryopreserved. MODEL NUMBER 3737 COX-1 N OM EN CLATURE CONSTITUTIVE KNOCK OUT MIXED C57BL/6 AND 129P2 BACKGROUND • Contains a disruption of the Ptgs1 gene, one of the prostaglandin endoperoxide synthase/ cyclooxygenase genes, preventing synthesis of the cyclooxygenase-1 (COX-1) protein. reduced inflammatory response to arachidonic acid, but not to other inflammatory agents. • Mice develop normally, appear healthy and do not exhibit gross or microscopic gastric lesions. • Homozygous mice have a significantly B6;129P2-Ptgs1tm1Unc • Useful to study cyclooxygenase inhibitors and NSAIDs and to examine the role of cyclooxygenae in inflammatory disease. • Cryopreserved. MODEL NUMBER 2180 TO ORDER US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Immunology and Inflammation IMMUNOLOGY AND INFLAMMATION TACONIC BIOSCIENCES COX-2 N OM ENCLATURE B6;129P2-Ptgs2tm1Unc CONSTITUTIVE KNOCK OUT MIXED C57BL/6 AND 129P2 BACKGROUND • Contains a disruption of the Ptgs2 gene, one of the prostaglandin endoperoxide synthase/ cyclooxygenase genes, preventing synthesis of the cyclooxygenase-2 (COX-2) protein. • Homozygotes develop peritoneal lesions and exhibit severe, progressive renal pathology and lesions of varying severity that cause a progressive deterioration with aging. • Homozygotes exhibit normal inflammatory response to bacterial assault and to arachidonic acid and other inflammatory agents. • Useful to examine the redundant and compensatory responses of the cyclooxygenase gene, to study cyclooxygenase inhibitors and NSAIDs and to examine the role of COX enzymes in inflammatory disease. • Cryopreserved. MODEL NUMBER 2181 Fcer1g (FcRγ) CONSTITUTIVE KNOCK OUT • Deficient in the γ chain subunit of the FcgRI, FcgRIII and FceRI receptors. • The deleted gamma chain subunit is essential for cell surface expression of Fc receptors. • Macrophages, neutrophils, mast cells, basophils and NK cells are functionally impaired, due to the lack of the Fc receptors. • The mice have normal T cell thymic development and peripheral T cell function. • Useful in determining the role of structurally similar Fc receptors in mediating effector immune responses and studying the pleiotropic role of the γ chain subunit. immunodeficiency making them useful for studies to distinguish the role of the Fc receptors in antibodymediated effector responses and to evaluate the contribution of IgG and IgE triggered effector pathways. • Mice exhibit several different types of C57BL/6 BACKGROUND BALB/c BACKGROUND THESE MICE CARRY THE H2b HAPLOTYPE THESE MICE CARRY THE H2d HAPLOTYPE NOMENCL AT URE N OM EN CLATUR E B6.129P2-Fcer1gtm1Rav N12 C.129P2(B6)-Fcer1gtm1Rav N12 MODEL NUMBER 583 MODEL NUMBER 584 Fcgr2b (FcγRII) CONSTITUTIVE KNOCK OUT • Deficient in FcgRIIβ protein, which is a low affinity immunoglobulin G receptor. • The FcgRIIβ protein inhibits the activation of disparate effector functions such as phagocytosis, antibody dependent cytotoxicity and release of inflammatory mediators. It is also known to function as an inhibitory receptor on B cells and mast cells. • This inhibitory pathway for activation of several immune effector responses is dysfunctional, resulting in the inability to regulate antibody levels in response to antigenic stimuli dependent on IgG immune complexes. • Useful for studying the feedback inhibition pathways that regulate antibody production and in studies of allergic and autoimmune disorders. C57BL/6 BACKGROUND BALB/c BACKGROUND THESE MICE CARRY THE H2b HAPLOTYPE THESE MICE CARRY THE H2d HAPLOTYPE NOMENCL AT URE N OM EN CLATUR E B6.129S4-Fcgr2btm1TtK N12 C.129S4(B6)-Fcgr2btm1TtK/cAnNTac N12 MODEL NUMBER 580 MODEL NUMBER 579 DISCUSS YOUR NEEDS US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Immunology and Inflammation IMMUNOLOGY AND INFLAMMATION TACONIC BIOSCIENCES HLA-A1 N OM EN CLATURE CB6F1-Tg(HLA-A*0101/H2-Kb)A1.01 RANDOM TRANSGENIC CB6F1 BACKGROUND • Carries a transgene consisting of fragments of the human HLA-A*0101 gene and mouse H2-Kb gene which encodes a chimeric class I molecule consisting of the human HLA-A1 leader, α1 and α2 domains ligated to the murine α3, transmembrane and cytoplasmic H2-Kb domains. safety and immunogenicity testing, as well as research directed towards oncology and autoimmune disorders. • Expresses the chimeric HLA-A1 class I molecule on the surface of T and B cells. • Represents the human HLA-A1 supertype. • Permits identification of epitopes restricted to the HLA-A1 supertype. • Useful for infectious disease research, vaccine development and testing, MODEL NUMBER 9662 HLA-A2.1 N OM EN CLATURE CB6F1-Tg(HLA-A*0201/H2-Kb)A*0201 RANDOM TRANSGENIC CB6F1 BACKGROUND • Carries a transgene consisting of fragments of the human HLA-A*0201 gene and mouse H2-Kb gene which encodes a chimeric class I molecule consisting of the human HLA-A2.1 leader, α1 and α2 domains ligated to the murine α3, transmembrane and cytoplasmic H2-Kb domains. safety and immunogenicity testing as well as research directed towards oncology and autoimmune disorders. • Expresses the chimeric HLA-A2.1 class I molecule on the surface of T and B cells. • Represents the human HLA-A2 supertype. • Permits identification of epitopes restricted to the HLA-A2 supertype. • Useful for infectious disease research, vaccine development and testing, MODEL NUMBER 9659 HLA-A11 N OM EN CLATURE CB6F1-Tg(HLA-A*1101/H2-Kb)A11.01 RANDOM TRANSGENIC CB6F1 BACKGROUND • Carries a transgene consisting of fragments of the human HLA-A*1101 gene and mouse H2-Kb gene which encodes a chimeric class I molecule consisting of the human HLA-A11 leader, α1 and α2 domains ligated to the murine α3, transmembrane and cytoplasmic H2-Kb domains. • Expresses the chimeric HLA-A11 class I molecule on the surface of T and B cells. • Represents the human HLA-A3 supertype. safety and immunogenicity testing as well as research directed towards oncology and autoimmune disorders. • Permits identification of epitopes restricted to the HLA-A11 supertype. • Useful for infectious disease research, vaccine development and testing, MODEL NUMBER 9660 TO ORDER US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Immunology and Inflammation IMMUNOLOGY AND INFLAMMATION TACONIC BIOSCIENCES HLA-A24 N OM ENCLATURE CB6F1-Tg(HLA-A*2402/H2-Kb)A24.01 RANDOM TRANSGENIC CB6F1 BACKGROUND • Carries a transgene consisting of fragments of the human HLA-A*2402 gene and mouse H2-Kb gene which encodes a chimeric class I molecule consisting of the human HLA-A24 leader, α1 and α2 domains ligated to the murine α3, transmembrane and cytoplasmic H2-Kb domains. • Expresses the chimeric HLA-A24 class I molecule on the surface of T and B cells. • Represents the human HLA-A24 supertype. safety and immunogenicity testing as well as research directed towards oncology and autoimmune disorders. • Permits identification of epitopes restricted to the HLA-A24 supertype. • Useful for infectious disease research, vaccine development and testing, MODEL NUMBER 9663 HLA-B7 N OM ENCLATURE CB6F1-B2mtm1Unc Tg(B2M)55Hpl Tg(HLA-B*0702/H2-Kb)B7.xx CONSTITUTIVE KNOCK OUT / RANDOM TRANSGENIC CB6F1 BACKGROUND • Carries a transgene consisting of fragments of the human HLA-B*0702 gene and mouse H2-Kb gene which encodes a chimeric class I molecule consisting of the human HLA-B7 leader, α1 and α2 domains ligated to the murine α3, transmembrane and cytoplasmic H2-Kb domains. • Expresses the chimeric HLA-B7 class I molecule on the surface of T and B cells. • Represents the human HLA-B7 supertype. safety and immunogenicity testing as well as research directed towards oncology and autoimmune disorders. • Permits identification of epitopes restricted to the HLA-B7 supertype. • Useful for infectious disease research, vaccine development and testing, MODEL NUMBER 9661 HLA-B44 N OM ENCLATURE CB6F1-Tg(HLA-B*4002/H2-Kb)B44.01 RANDOM TRANSGENIC CB6F1 BACKGROUND • Carries a transgene consisting of fragments of the human HLA-B*4002 gene and mouse H2-Kb gene which encodes a chimeric class I molecule consisting of the human HLA-B44 leader, α1 and α2 domains ligated to the murine α3, transmembrane and cytoplasmic H2-Kb domains. • Expresses the chimeric HLA-B44 class I molecule on the surface of T and B cells. safety and immunogenicity testing as well as research directed towards oncology and autoimmune disorders. • Represents the human HLA-B44 supertype. • Permits identification of epitopes restricted to the HLA-B44 supertype. • Useful for infectious disease research, vaccine development and testing, MODEL NUMBER 9664 DISCUSS YOUR NEEDS US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Immunology and Inflammation IMMUNOLOGY AND INFLAMMATION TACONIC BIOSCIENCES Abb Knockout/ Transgenic HLA-DR4 N OM EN CLATURE B6.129S2-H2-Ab1tm1Gru Tg(HLA-DRA/H2-Ea, HLA-DRB1* 0401/H2-Eb)1Kito CONSTITUTIVE KNOCK OUT / RANDOM TRANSGENIC C57BL/6 BACKGROUND • The HLA-DR4 allele is associated with the development of autoimmune diseases like rheumatoid arthritis and multiple sclerosis. • Expresses a hybrid MHC class II molecule with the peptide binding domains of human HLA-DRA and HLA-DRB*0401 and the membrane proximal domains of mouse I-E (H2-E). • Useful for studies of autoimmune disease and vaccine research. MODEL NUMBER 4149 Jh N OM EN CLATURE STOCK Igh-Jtm1Dhu N?+N2 CONSTITUTIVE KNOCK OUT STOCK BACKGROUND • Carries a deletion of the endogenous murine J segments of the Ig heavy chain locus. • In homozygotes, all four JH gene segments are absent, resulting in cells that cannot produce a complete, recombined version of the variable region of the heavy chain. • Have no detectable IgM or IgG in the sera. • A low level (about 1% of normal) of rearrangement of the light chain kappa gene family is detected in total bone marrow. • Cells of the B lineage are drastically altered both in developmental progression and in cell quantity. • Contain no mature (immunoglobulinbearing) B lymphocytes in the spleen, bone marrow, lymph nodes, peripheral blood or peritoneum. • Useful for studying non-B cell activity in pathogen-induced disease and mechanisms of antibody gene assembly and expression. • T lymphocyte development appears to proceed normally, based on surface phenotype and quantity of cells in the spleen; splenic lymphocytes are enriched for T cells due to the B cell deficit. • Provides a null background useful for gene replacement experimentation in normal immune response and autoimmune diseases. MODEL NUMBER 1147 Rag2/II2rg Double Knockout N OM EN CLATURE B10;B6-Rag2tm1Fwa IIrgtm1Wjl CONSTITUTIVE KNOCK OUT MIXED BACKGROUND • Lacks mature T, B and NK cells. • Applications include xenografts, transplantation of allogeneic or xenogeneic stem cells and research on the role of NK cells in host resistance to tumors and infectious agents. • Not appropriate for studies involving engraftment of human hematopoietic stem cells. • Very useful for transplanting allogeneic or xenogeneic stem cells which are often rejected by NK cells. MODEL NUMBER 4111 TO ORDER US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Immunology and Inflammation IMMUNOLOGY AND INFLAMMATION TACONIC BIOSCIENCES Rag2 CONSTITUTIVE KNOCK OUT T & B CELL DEFICIENT MODEL • Contains a disruption of the recombination activating gene 2 (Rag2). • Homozygous mice exhibit total inability to initiate V(D)J rearrangement and fail • Rag2 knockouts may be used for adoptive transfer-induced IBD studies. to generate mature T or B lymphocytes. • Useful for vaccine development, transplantation studies and hematopoiesis research. 129S6 BACKGROUND B6.SJL-Ptprc a BACKGROUND NOMENCL AT URE N OM EN CLATUR E 129S6/SvEvTac-Rag2tm1Fwa B6.SJL(129S6)-Ptprca/BoyCrTac-Rag2tm1Fwa N10 • The 129S6 strain was the original strain in which the Rag2 targeted mutation was created. • The Ptprc a marker on hematopoietic cells of this congenic strain allows for their identification in immunological adoptive transfer experiments. • Similar to C57BL/6 with the H2b haplotype but carries Ptprc a and Pep3b genes from SJL strain. • Cryopreserved. MODEL NUMBER RAG2 MODEL NUMBER 461 BALB/c BACKGROUND C57BL/6NTac BACKGROUND NOMENCL AT URE N OM EN CLATUR E B6.129S6-Rag2tm1Fwa N12 C.129S6(B6)-Rag2tm1Fwa N12 • Backcrossed twelve generations (N12) to a BALB/cAnNTac. • Carries the H2d haplotype. MODEL NUMBER 601 • Backcrossed twelve generations (N12) to a C57BL/6NTac inbred background. • Carries the H2b haplotype. MODEL NUMBER RAGN12 Rag2/OT-I N OM ENCLATURE B6.129S6-Rag2tm1Fwa Tg(TcraTcrb)1100Mjb CONSTITUTIVE KNOCK OUT/ RANDOM TRANSGENIC • Carries a transgene that encodes a T cell receptor (Vα2-Jα26 and Vβ5-Dβ2-Jβ.6) specific for a chicken ovalbumin peptide fragment (257-264) presented by the MHC class I molecule H2-Kb. therefore does not develop mature T or B cells expressing endogenous T cell receptors. • Virtually all peripheral CD8+ cells express the transgene. • Useful as a source of homogeneous donor CD8+ T cells for in vivo adoptive transfer studies to investigate T cell development, activation, memory and tolerance. • Deficient in the recombination reactivating gene 2 (Rag2) and MODEL NUMBER 2334 DISCUSS YOUR NEEDS US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Immunology and Inflammation IMMUNOLOGY AND INFLAMMATION TACONIC BIOSCIENCES Rag2/OT-II N OM EN CLATURE B6.129S6-Rag2tm1Fwa Tg(TcraTcrb)425Cbn CONSTITUTIVE KNOCK OUT/ RANDOM TRANSGENIC C57BL/6 BACKGROUND • Carries a transgene that encodes a T cell receptor (Vα2 and Vβ5) specific for a chicken ovalbumin peptide fragment (323-339) presented by the MHC class II molecule H2-Ab1 (I-Ab). • Deficient in the recombination reactivating gene 2 (Rag2) and does not develop mature T or B cells expressing endogenous T cell receptors • Useful as a source of homogeneous donor CD4+ T cells for in vivo adoptive transfer studies to investigate T cell development, activation, memory and tolerance. • Virtually all peripheral CD4+ cells express the transgene. MODEL NUMBER 1896 T-bet CONSTITUTIVE KNOCK OUT HYPERSENSITIVE IMMUNE SYSTEM • Altered cytokine production and differentiation of T helper cells. • Decreased NK cell function. C57BL/6 BACKGROUND • Immune system hypersensitivity makes this an excellent model of asthma, Crohn’s disease, colitis, cancer metastasis, autoimmune disorders, and inflammation. • Cryopreserved. BALB/c BACKGROUND N O M ENCL ATU RE N OM EN CLATUR E B6.129S6-Tbx21tm1Glm N10 C.129S6(B6)-Tbx21tm1Glm N10 MODEL NUMBER 3427 MODEL NUMBER 3469 TNF-α N OM EN CLATURE B6.Cg(SJL)-Tg(TNF) N21+? RANDOM TRANSGENIC INFLAMMATORY ARTHRITIS MODEL C57BL/6NTac BACKGROUND • Expresses the human tumor necrosis factor α (TNF-α) transgene, a cytokine implicated in the pathogenesis of human rheumatoid arthritis. • Exhibits severe chronic arthritis of the forepaws and hind paws, as shown by gross observation and histological analysis by approximately 20 weeks of age. • A useful model for studying inflammatory arthritis which does not require experimental manipulation. • Suitable for efficacy testing of biosimilars. MODEL NUMBER 1006 TO ORDER US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Immunology and Inflammation IMMUNOLOGY AND INFLAMMATION TACONIC BIOSCIENCES EMERGING MODELS The Emerging Models program includes distribution of investigatorsponsored models which are bred and distributed by Taconic. Since the sponsor sets distribution requirements for each of the Emerging Models, customers may be required to execute an MTA before certain models are delivered. CIEA NOG mouse ® SPONTANEOUS MUTANT/CONSTITUTIVE KNOCK OUT NOD BACKGROUND • The CIEA NOG mouse® represents a new generation of immunodeficient models. This severely immunocompromised mouse carries the scid mutation and a targeted mutation of the Il2rg gene on the NOD/ShiJic genetic background. • The functional knockout of the Il-2Rγ chain results in reduction of residual innate immunity of the NOD/ShiJic background and superior engraftment of human cells and tissues compared to any other immune deficient model. • Lacks mature T, B and NK cells. • Reduced complement activity. • Dysfunctional macrophages and dendritic cells. • Deficiencies in immune signaling, including impaired cytokine production. • Displays very low incidence of lymphoma (unlike NOD scid model). • The Il2rg gene is sex-linked. • Applications in basic and translational research involving xenotransplantation of normal human and cancer cell lines and tissues, N OM EN CLATURE NOD.Cg-Prkdc scid Il2rg tm1Sug/JicTac immunity and the development of the immune system, hematopoiesis, stem cell research, infectious disease studies, regeneration of damaged tissues, development of new immune system engrafted models. • Sponsored by the Central Institute for Experimental Animals and In-Vivo Science International. • The CIEA NOG mouse® has been shown to be the model of choice for the grafting and reconstitution of human tissues. NO MTA OR LICENSE FEES REQUIRED FOR PURCHASE MODEL NUMBER NOG DISCUSS YOUR NEEDS US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Immunology and Inflammation IMMUNOLOGY AND INFLAMMATION TACONIC BIOSCIENCES CIEA BRG mouse N OM EN CLATURE C.Cg-Rag2tm1Fwa Il2rgtm1Sug/JicTac CONSTITUTIVE KNOCK OUT • Immunodeficient model lacking mature T, B, and NK cells. • Higher radiation tolerance due to Rag2 mutation compared to scid models (similar to wild type mice). • Model is completely congenic on BALB/c background, the preferred strain background for many immunology studies. • Applications in studies on immune system engraftment, infectious diseases and autoimmune diseases as well as cancer xenografts. • Sponsored by the Central Institute for Experimental Animals and In-Vivo Science International. NO MTA OR LICENSE FEES REQUIRED FOR PURCHASE MODEL NUMBER 11503 LIGHT PRODUCING TRANSGENIC ANIMALS® (LPTA®) Reporter models expressing luciferase under the control of various promoters, for use in bioluminescent imaging applications. β-actin-luc RANDOM TRANSGENIC • Constitutively expresses luciferase in all tissues. • Basal expression of the reporter is highest in skeletal muscle, thymus, skin, FVB BACKGROUND heart, bone, pancreas, and is detectable in all tissues, including white blood cells. • The reporter is constitutively expressed and is not significantly inducible. B6;FVB ALBINO BACKGROUND NO MENCL ATU RE FVB/NTac-Tg(Actb-luc)46Xen • Useful as a donor animal for studying the transplantation of various tissue types. N OM EN CLATUR E B6;FVB-Tyr c-2J Tg(Actb-luc)46Xen • SNP testing has shown that the strain background is equivalent only to 4-5 backcrosses onto B6 albino, so the background is designated as B6;FVB. MODEL NUMBER 10498 MODEL NUMBER 10500 TO ORDER US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Immunology and Inflammation IMMUNOLOGY AND INFLAMMATION TACONIC BIOSCIENCES Gfap-luc N OM ENCLATURE FVB/N-Tg(Gfap-luc)53Xen RANDOM TRANSGENIC FVB BACKGROUND • Expresses luciferase under control of the Gfap promoter, which is inducible following CNS injury. • Please inquire for timeline and pricing for F1 hybrids of the Gfap-luc and B6 albino mice for use in EAE studies. • As a reporter for neuroinflammation, luciferase expression provides an additional readout beyond simple clinical score in EAE studies with this model. MODEL NUMBER 10501 NFκB-RE-Luc N OM ENCLATURE BALB/c-Tg(Rela-luc)31Xen RANDOM TRANSGENIC BALB/c BACKGROUND • The model provides for the rapid study of transcriptional regulation of the NFκB gene. • Useful in studying sepsis, arthritis, inflammatory bowel disease, apoptosis, tumor development, NFκB gene regulation and the treatment of inflammatory diseases and cancer. MODEL NUMBER 10499 ADDITIONAL LPTA® MODELS AVAILABLE FROM TACONIC’S CRYOPRESERVED REPOSITORY. MODEL NAME 10627 Gadd45b-luc 10628 Epx-luc 10629 Saa1-luc 10630 IL-2-luc 10646 Cox2-luc 10647 Tnfa-luc 10650 IkBa-luc Tnf-α Knockout CONSTITUTIVE KNOCK OUT C57BL/6 BACKGROUND • Altered susceptibility to infection, immune responses and inflammatory responses. LUDWIG INSTITUTE SPONSORED EMERGING MODEL MODEL NUMBER 1921 DISCUSS YOUR NEEDS US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Immunology and Inflammation IMMUNOLOGY AND INFLAMMATION TACONIC BIOSCIENCES Human Immune System Engrafted Mice The super immunodeficient CIEA NOG mouse® is the ideal model for engraftment of human hematopoetic stem cells, and therefore the model of choice for immune system engraftment. NOG mice reconstituted with a variety of human tissues represent a valuable tool for basic research involving the human immune system. Engrafted NOG mice enable efficacy testing of immunotherapies as well as the unprecedented ability to study tumor specific immune cell activation. Taconic offers study ready cohorts of hematopoietic stem cell engrafted NOG mice, as well as expert scientific consultation on use of the CIEA NOG mouse® for engraftment and reconstitution with human tissues. CIEA NOG mouse ® IMMUNOTHERAPY / VACCINE INFLAMMATION / ALLERGY GvHD / TRANSPLANTATION AUTOIMMUNE DISEASE IMMUNOTHERAPY / VACCINE SAFETY ASSESSMENT HEMATOPOIESIS APPLICATIONS FOR HUMAN IMMUNE SYSTEM MICE • Hematopoiesis and immune cell development • Infectious disease and humanspecific pathogens • Efficacy testing of immunotherapy and checkpoint blocking antibodies INFECTIOUS DISEASE • Safety assessment for new therapeutics + human hematopoietic stem cells (huNOG) • Transplantation and Graft vs Host Disease (GvHD) + human peripheral blood mononuclear cells (huPBMC-NOG) • Vaccine development + human liver, thymus and hematopoietic stem cells (BLT-NOG) • Inflammation and allergy • Autoimmune disease For additional information on these models, visit Taconic.com/humanimmune-system-engrafted-mice TO ORDER US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Immunology and Inflammation IMMUNOLOGY AND INFLAMMATION TACONIC BIOSCIENCES huPBMC-NOG NOG MICE ENGRAFTED WITH HUMAN PBMCs (PERIPHERAL BLOOD MONONUCLEAR CELLS) • Model for investigation of adult/ mature cell populations. • Use is limited to short term studies. • GvHD response can be used as a screening system for T cell modulating drugs. • Available with normal or patientderived PBMCs. huNOG NOG MICE ENGRAFTED WITH HUMAN CD34 + HEMATOPOIETIC STEM CELLS (HSCs) • Stable engraftment of multiple cell lineages by 12-16 weeks post-injection. • Only mice with ≥25% hCD45+ in peripheral blood are delivered. • Long-term studies possible. huNOG ARE AVAILABLE OFF-THESHELF! PLACE YOUR ORDER NOW FOR IMMEDIATE DELIVERY. BLT-NOG NOG MICE INJECTED WITH CD34 + HEMATOPOIETIC STEM CELLS (HSCs) AND SURGICALLY ENGRAFTED WITH DONOR MATCHED THYMUS AND LIVER SECTIONS • Stable engraftment of multiple cell lineages, with enhanced T and B cell function. • Particularly suited to vaccine studies, antibody generation studies, and any study for modeling human B cell responses. LICENSING: NO MTA OR LICENSE FEE IS REQUIRED FOR ANY OF THE MODELS FEATURED ON THIS PAGE. DISCUSS YOUR NEEDS US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Immunology and Inflammation IMMUNOLOGY AND INFLAMMATION Take Your Research Further GEMS DESIGN PRECISION RESEARCH MODELS GEMS MANAGEMENT Taconic Biosciences GEMs Design empowers our clients to develop research models specifically suited to the unique needs of their discovery and development studies or therapeutic programs. Research organizations demand precision tools that better reflect human physiology. Taconic Biosciences leads the field delivering innovative solutions to meet these continually evolving needs. Our core competencies include the delivery of complex strategies that both integrate human genetic sequences and engraft human cells and tissues into custom mouse and rat models. Taconic’s fully integrated GEMs Management brings innovative models from design to study-ready cohorts with unprecedented speed and transparency. • Human Gene Replacement • Genotyping and Molecular Analysis • Gene Inactivation • Gene Mutation or Replacement • CRISPR Gene Editing • Transgene Expression • miRNA Expression • Cohort Production Packages • Human Cell and Tissue Engraftment • Embryology • Rapid Colony Expansion • Contract Breeding • Surgical Services • Tissue Collection • Microbiome and Germ-Free Research Models and Services CHOOSE TACONIC TALK TO A SCIENTIST For more than 60 years, Taconic has anticipated the needs of the scientific community to deliver models and services that meet the diverse needs of biomedical and biopharmaceutical researchers. Our scientific teams are happy to meet and talk with you about the most efficient way to achieve your study goals. Working in partnership with clients the world over, our scientific teams offer expert advice that can help you speed up your research and reduce your overall costs. Today that forward thinking and commitment to working collaboratively has resulted in a client-centric environment infused with a knowledge bank that allows you to select the optimum model for your study based on informed insight into the generation of genetically engineered mouse and rat models. TALK TO A REPRESENTATIVE For general information, you can talk to a member of our customer service team. Our customer service team is here to help you make the right decisions and get the models you need fast. Contact us at [email protected] YOUR COLLABORATIVE PARTNER As a full-service biosciences company, Taconic can help you acquire, test, develop, breed, cryopreserve, prepare, and distribute highly relevant research lines worldwide. Whether you require custom genetically engineered, cell or tissue engrafted models or traditional models, Taconic’s scientists will partner with you to rapidly and efficiently deliver the highest quality models. VISIT TACONIC.COM For more information on the entire Taconic portfolio of products and services designed to help further your research, visit Taconic.com ©Taconic Biosciences, Inc. All rights reserved. Contents of this publication may not be reproduced in any form without prior permission. US: 1-888-822-6642 EU: +45 70 23 04 05 [email protected] TACONIC.COM 0516