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Oncology MODELS AND SERVICES DESIGNED TO TAKE YOUR STUDY FURTHER ONCOLOGY TACONIC BIOSCIENCES Oncology Evaluating the response of translational rodent models to new cancer therapies is the key to developing innovative treatment options. The super immunodeficient CIEA NOG mouse® is the ideal model for engraftment of human cells, and therefore the model of choice for combined immune system and tumor engraftment immuno-oncology experiments. Taconic Biosciences offers a comprehensive portfolio of translational rodent models to accelerate and enhance your research in the field of oncology. Mouse models available exclusively from Taconic include human immune system engrafted mice for tumor grafting and therapeutics testing, spontaneous tumor models for breast and colon cancer research, and a wide variety of immunodeficient mice, including the super immunodeficient CIEA NOG mouse®. Taconic also provides integrated model generation and breeding services to accelerate drug discovery and development timelines. DISCUSS YOUR NEEDS US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Oncology | 2 ONCOLOGY TACONIC BIOSCIENCES TABLE OF CONTENTS HUMAN IMMUNE SYSTEM ENGRAFTED MODELS�������������������������������������������������������������������5 SUPER IMMUNODEFICIENT NOG MODELS��������������������������������������������������������������������������������7 IMMUNODEFICIENT MODELS�����������������������������������������������������������������������������������������������������������9 Nudes������������������������������������������������������������������������������������������������������������������������������������������������������ 9 SCIDs������������������������������������������������������������������������������������������������������������������������������������������������������� 11 Rag2 Models���������������������������������������������������������������������������������������������������������������������������������������� 12 MODELS WITH MULTIPLE IMMUNODEFICIENCIES��������������������������������������������������������������� 13 MODELS FOR SYNGENEIC TUMOR EXPERIMENTS�������������������������������������������������������������� 14 SPONTANEOUS TUMOR MODELS������������������������������������������������������������������������������������������������ 16 COMPARISON CHART OF ONCOLOGY MOUSE AND RAT MODELS����������������������������20 INTEGRATED CUSTOM MODEL GENERATION AND BREEDING SOLUTIONS����������� 21 TO ORDER 3 | Oncology US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] ONCOLOGY TACONIC BIOSCIENCES TACONI C OF F ER S HUM AN I M M U NE SYSTEM E NGRAF TED M OD EL S CIEA NOG mouse ® Immunodeficient mice carrying a reconstituted human immune system The super immunodeficient CIEA NOG mouse® is the ideal model for engraftment of human cells, and therefore the model of choice for combined immune system and tumor engraftment immunooncology experiments. When reconstituted with various human tissue sources, NOG mice are indispensable for basic research probing the human immune system. Engrafted NOG mice enable efficacy testing of immunotherapies as well as the unprecedented ability to study tumor specific modulation of the immune system. Taconic offers study-ready cohorts of hematopoietic stem cell-engrafted NOG mice. In addition to these models, Taconic offers access to scientific expertise on use of the CIEA NOG mouse® for engraftment and reconstitution with human tissues. HOW CAN IMMUNE SYSTEM ENGRAFTED NOG MICE BE USED? Immune system engrafted mouse models are excellent tools to evaluate the effect of human immune cells in preclinical oncology: • Assessment of therapeutic immunomodulatory activities • Evaluation of antitumor activity related to antibody dependent cell cytotoxicity (ADCC) • Analysis of innate and adaptive immunity • Cytokine readouts These models are also excellent tools for other research application, such as: • Immuno-Oncology Research • GvHD (Graft versus Host Disease) • T cell activation model • B cell depletion studies • Autoimmune disease • Allergy • Inflammation • HIV Research • Vaccine development • Transplantation • Study of hematopoiesis DISCUSS YOUR NEEDS US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Oncology | 4 ONCOLOGY 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 MICE ARE AVAILABLE OFF-THE-SHELF! PLACE YOUR ORDER NOW FOR IMMEDIATE DELIVERY. huNOG-EXL NOG-EXL (HGM-CSF/HIL3-NOG) MICE ENGRAFTED WITH HUMAN CD34 + HEMATOPOIETIC STEM CELLS (HSCs) • Stable engraftment of multiple cell lineages, with improved myeloid cell differentiation. • Only mice with ≥25% hCD45+ in peripheral blood are delivered. • Long-term engraftment enables long-term studies. huNOG-EXL MICE ARE AVAILABLE OFF-THE-SHELF! PLACE YOUR ORDER NOW FOR IMMEDIATE DELIVERY. LICENSING: NO MTA OR LICENSE FEE IS REQUIRED FOR ANY OF THE MODELS FEATURED ON THIS PAGE. TO ORDER 5 | Oncology US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] ONCOLOGY TACONIC BIOSCIENCES H E M ATO P O IE S IS A ND HUM AN I M M U N E SYST E M ENG RAFTED MICE HEMATOPOIETIC STEM CELL IL-1 IL-3 GM-CSF SCF COMMON LYMPHOID PROGENITOR COMMON MYELOID PROGENITOR IL-2 IL-7 IL-12 SDF-1 GM-CSF IL-1 IL-6 IL-2 IL-7 IL-4 MYELOBLAST TNK PROGENITOR B LYMPHOCYTE SCF G-CSF GM-CSF IL-3 IL-6 BASOPHIL SCF G-CSF GM-CSF IL-3 IL-6 GM-CSF IL-3 IL-5 NEUTROPHIL EOSINOPHIL huNOG-EXL (hGM-CSF/hIL-3 NOG) SCF M-CSF G-CSF GM-CSF IL-3 IL-6 MONOCYTE hIL-6 NOG IL-2 IL-7 IL-15 IL-7 NK CELL hIL-2 NOG, hIL-15 NOG T LYMPHOCYTE huNOG DISCUSS YOUR NEEDS US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Oncology | 6 ONCOLOGY TACONIC BIOSCIENCES S U PE R I MMU NO DEF ICIENT N O G M O DE LS CIEA NOG mouse® N OM EN CLATURE T, B & NK CELL DEFICIENT MOUSE WITH IMPAIRED MYELOID FUNCTIONS • The CIEA NOG mouse® is a super immune deficient mouse with unparalleled potential to engraft human cells and tissues. • 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 IL2 receptor common gamma chain (IL2rg) 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. • Lack of mature T, B and NK cells, reduced complement activity, dysfunctional macrophages and dendritic cells, and deficiencies in immune signaling, including impaired cytokine production. NOD.Cg-Prkdcscid Il2rgtm1Sug/JicTac • The polymorphism of Sirpa allows the mouse SIRPA to bind human CD47, preventing activation of recipient macrophages to engulf human cells therefore making it an ideal model for human immune system engraftment and PDX. • Excellent choice for xenograft studies using cell lines with poor take rates in nudes or scids, or for engraftment of patient-derived tumors. • The best choice for human immune system engraftment mice, with successful engraftment of various tissues such as PBMCs or umbilical cord blood stem cells. • Test therapeutic antibodies and immune-modulating treatments by combining immune system engraftment of the immune system with xenograft of tumor cell lines or patient-derived tumors. • Displays a very low incidence of lymphoma, unlike NOD scid model. • The Il2rg gene is X-linked, so male knockouts are hemizygous for the Il2rg mutant allele. • Sponsored by the Central Institute for Experimental Animals (CIEA) and In-Vivo Science International. • Applications in research involving cancer, infectious disease (HIV, malaria), immuno-oncology, CAR-T, iPS, and humanization immune system engraftment. • Now available pre-engrafted with human hematopoietic stem cell (hHSC) as huNOG for immediate delivery at 16 weeks post-engraftment. MODEL NUMBER NOG NOG-EXL (hGM-CSF/hIL-3 NOG) T, B & NK CELL DEFICIENT MOUSE WITH IMPAIRED MYELOID FUNCTIONS • NOG mouse expressing human GM-CSF and IL-3. • Supports higher overall engraftment and superior myeloid cell differentiation after human HSC engraftment. • Now available pre-engrafted with HSCs as huNOG-EXL for immediate delivery at 10 weeks post-engraftment. N OM EN CLATURE NOD.Cg-Prkdcscid Il2rgtm1Sug Tg(SV40/HTLV-IL3,CSF2)10-7Jic/JicTac • May be a suitable host for human acute myeloid leukemia (AML) xenografts that are dependent on human GM-CSF and human IL-3. • The polymorphism of Sirpa allows the mouse SIRPA to bind human CD47, preventing activation of recipient macrophages to engulf human cells therefore making it an ideal model for human immune system engraftment and PDX. • Excellent choice for xenograft studies using cell lines with poor take rates in nudes or scids, or for engraftment of patient-derived tumors that requires human GM-CSF or human IL-3. MODEL NUMBER 13395 TO ORDER 7 | Oncology US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] ONCOLOGY TACONIC BIOSCIENCES hIL-2 NOG N OMENCLATURE T, B & NK CELL DEFICIENT MOUSE WITH IMPAIRED MYELOID FUNCTIONS • NOG mouse expressing human IL-2 cytokine. • Predominant differentiation of human NK cells following hHSC engraftment. NOD.Cg-Prkdcscid Il2rgtm1Sug Tg(CMV-IL6)4-2Jic/JicTac • Excellent choice for xenograft studies using cell lines with poor take rates in nudes or scids, or for engraftment of patient-derived tumors or tumor infiltrating lymphocytes that requires human IL-2. MODEL NUMBER 13440 hIL-6 NOG N OMENCLATURE T, B & NK CELL DEFICIENT MOUSE WITH IMPAIRED MYELOID FUNCTIONS • NOG mouse expressing human IL-6 cytokine. • Enhanced expansion of human monocytes following hHSC engraftment. NOD.Cg-Prkdcscid Il2rgtm1Sug Tg(CMV-IL6)1-1Jic/JicTac • May be a suitable host for human IL-6 dependent tumor such as multiple myeloma (MM) xenografts. MODEL NUMBER 13686 hIL-15 NOG N OMENCLATURE T, B & NK CELL DEFICIENT MOUSE WITH IMPAIRED MYELOID FUNCTIONS • NOG mouse expressing human IL-15 cytokine. NOD.Cg-Prkdcscid Il2rgtm1Sug Tg(CMV-IL2/IL15)1-1Jic/JicTac • Engraftment and expansion of human NK cells following engraftment with CD56+ NK cells derived from PBMC. MODEL NUMBER 13683 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] Oncology | 8 ONCOLOGY TACONIC BIOSCIENCES IM M UNO DE FIC IENT M OD ELS NUDES THE AUTOSOMAL RECESSIVE NUDE GENE IN HOMOZYGOUS (NU/NU) MICE CAUSES THE LACK OF FUR AND AN ABNORMAL THYMUS. HETEROZYGOUS (NU/+) ANIMALS CARRY ONLY ONE COPY OF THE NUDE MUTATION AND HAVE HAIR. HETEROZYGOUS NUDES WERE ORIGINALLY THOUGHT TO HAVE NORMAL IMMUNE SYSTEMS, BUT IN FACT HAVE IMMUNE ALTERATIONS SUCH AS REDUCED BONE MARROW STEM CELLS AND LOWER THYMUS WEIGHTS. HETEROZYGOUS NUDES MAY BE USED IN PK/DOSING STUDIES. B6 nude N OM EN CLATURE B6.Cg/NTac-Foxn1nu NE10 T CELL DEFICIENT MOUSE • Foxn1nu mutation backcrossed to the C57BL/6NTac inbred strain for ten generations. MODEL NUMBER B6NU BALB/c nude N OM EN CLATURE C.Cg/AnNTac-Foxn1nu NE9 T CELL DEFICIENT MOUSE • Foxn1nu mutation backcrossed to the BALB/cAnN inbred strain for nine generations. MODEL NUMBER BALBNU NCr nude N OM EN CLATURE CrTac:NCr-Foxn1nu T CELL DEFICIENT MOUSE • 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. MODEL NUMBER NCRNU TO ORDER 9 | Oncology US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] ONCOLOGY TACONIC BIOSCIENCES NIH nude N OMENCLATURE NTac:NIH-Foxn1rnu T CELL DEFICIENT RAT • This immunodeficient rat model is ideal for studies requiring a larger tumor burden, studies which require imaging or studies which bridge oncology efficacy and PK/PD. • In this outbred immunodeficient model the vibrissae are present in the homozygous nude rat, but they are bent, with some short hairs on the head and occasionally on the rest of the body. • Good xenograft host for many cell lines. MODEL NUMBER NIHRNU NMRI nude N OMENCLATURE BomTac:NMRI-Foxn1nu T CELL DEFICIENT MOUSE • Foxn1nu mutation backcrossed to the NMRI outbred stock. • Widely-used as host for transplanted human tumors and for therapeutic studies on human tumors. • The NMRI nude has a relatively low take-rate for human breast tumors compared to other nude or immunodeficient mice. MODEL NUMBER NMRINU HRN™ nude N OMENCLATURE CrTac:NCr-Portm1Wolf Foxn1nu Tg(Alb-cre)21Mgn T CELL DEFICIENT MOUSE • The combination of the nude mutation and the HRN™ mutations permits xenograft studies in a mouse without liver P450 metabolism. • Useful when studying highly cleared chemotherapeutics, allowing efficacy testing without the need for multiple dosing or the use of constant infusion pumps. • Used to get a quick readout on the efficacy of your anticancer lead compounds without having to first work through PK issues. • A combination between Taconic’s leading outbred nude, the NCr nude, and the HRN™ transgenic mouse. MODEL NUMBER 9066 CRYOP RES ERVED DISCUSS YOUR NEEDS US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Oncology | 10 ONCOLOGY SCIDs TACONIC BIOSCIENCES SEVERE COMBINED IMMUNODEFICIENCY MICE HOMOZYGOUS FOR THE Prkdc scid MUTATION LACK BOTH T AND B CELLS DUE TO A DEFECT IN V(D)J RECOMBINATION. THIS FEATURE MAKES THESE MODELS IDEAL FOR ACCEPTING FOREIGN TISSUE TRANSPLANTS, INCLUDING HUMAN TUMORS. THESE MODELS ARE USED FOR TESTING NEW CANCER TREATMENTS, AND AS HOSTS FOR HUMAN IMMUNE SYSTEM TISSUES (I.E. SCID-HU). C.B-17 scid N OM EN CLATURE C.B-Igh-1b/IcrTac-Prkdcscid T & B CELL DEFICIENT MOUSE • The original congenic background strain on which Dr. Mel Bosma discovered the spontaneous scid mutation. • Available at two health designations: Defined Flora from gnotobiotic isolators and Restricted Flora™ from Isolated Barrier Units™. MODEL NUMBER CB17SC ICR scid N OM EN CLATURE T & B CELL DEFICIENT MOUSE IcrTac:ICR-Prkdcscid • Equivalent to the C.B-17 scid in severity of immunodeficiency, but this outbred background exhibits a significantly reduced incidence of spontaneous Ig production (leakiness). MODEL NUMBER ICRSC NOD scid N OM EN CLATURE T & B CELL DEFICIENT MOUSE • The scid mutation has been transferred onto a diabetes-susceptible Non-Obese Diabetic (NOD). NOD/MrkBomTac-Prkdcscid • The multiple defects in immunity unique to this model provide a very good system for reconstitution with human hematopoietic cells, resulting in excellent models for HIV-1 research and gene therapy. • Useful model for investigating increased tumor incidence, particularly lymphomas and thymic tumors. • Short life span of ~8-9 months due to lethal thymic lymphomas. • Does not develop spontaneous diabetes. MODEL NUMBER NODSC TO ORDER 11 | Oncology US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] ONCOLOGY TACONIC BIOSCIENCES Rag2 MODELS MICE HOMOZYGOUS FOR THE RAG2 NULL MUTATION EXHIBIT TOTAL INABILITY TO INITIATE V(D)J REARRANGEMENT AND FAIL TO GENERATE MATURE T OR B LYMPHOCYTES. NEVERTHELESS, THE RAG2 MOUSE HAS APPARENTLY NORMAL HEMATOPOIESIS. RAG2 KNOCKOUTS ARE USEFUL FOR VACCINE DEVELOPMENT, TRANSPLANTATION OR XENOGRAFT STUDIES, AND HEMATOPOIESIS RESEARCH. THE RAG2 MOUSE IS USEFUL IN EVALUATING THE FUNCTION OF SPECIFIC GENES AS THEY RELATE TO BONE MARROW TRANS-COMPLEMENTATION ASSAYS. Rag2 (129S6) T & B CELL DEFICIENT MOUSE N OMENCLATURE 129S6/SvEvTac-Rag2tm1Fwa • The 129S6 strain was the original strain in which the Rag2 targeted mutation was created. MODEL NUMBER RAG2 CRYOP RES ERVED Rag2 (BALB/c) T & B CELL DEFICIENT MOUSE N OMENCLATURE C.129S6(B6)-Rag2tm1Fwa N12 • Backcrossed twelve generations (N12) to the BALB/cAnNTac inbred strain. MODEL NUMBER 601 Rag2 (B6.SJL) T & B CELL DEFICIENT MOUSE N OMENCLATURE B6.SJL(129S6)-Ptprca/BoyCrTac Rag2tm1Fwa N10 • Similar to C57BL/6 with the H2b haplotype, but carries the Ptprca and Pep3b genes from the SJL strain (CD45.1). MODEL NUMBER 461 CRYOP RES ERVED Rag2 (C57BL/6) T & B CELL DEFICIENT MOUSE N OMENCLATURE B6.129S6-Rag2tm1Fwa N12 • Backcrossed twelve generations (N12) to the C57BL/6NTac inbred strain. MODEL NUMBER RAGN12 DISCUSS YOUR NEEDS US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Oncology | 12 ONCOLOGY TACONIC BIOSCIENCES M O D E L S W IT H MU LT IPLE IMM UNO DEF IC IE NC IES Scid-beige N OM EN CLATURE T, B & NK CELL DEFICIENT MOUSE • The mutations were backcrossed seven generations to the congenic C.B-17 background. C.B-Igh-1b/GbmsTac-Prkdcscid Lystbg N7 • 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. • It also carries the beige mutation which results in cytotoxic T cell and macrophage defects as well as selective impairment of NK cell functions. MODEL NUMBER CBSCBG Rag2/Il2rg Double Knockout Mouse N OM EN CLATURE B10;B6-Rag2tm1Fwa Il2rgtm1Wjl T, B & NK CELL DEFICIENT MOUSE • Useful for transplanting allogeneic or xenogeneic stem cells, which are often rejected by NK cells. • May be used in combination with parent Rag2 knockout model for defining the role of NK cells in host resistance to tumors and infectious agents. • May not be the best choice for experiments involving humanization of the immune system, since human hematopoietic stem cells do not engraft and differentiate well in strains on B6 or B6-related backgrounds. • The Il2rg gene is located on the X chromosome, so male knockouts are hemizygous for the Il2rg mutant allele. MODEL NUMBER 4111 CIEA BRG mouse N OM EN CLATURE T, B & NK CELL DEFICIENT • 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. C.Cg-Rag2tm1Fwa Il2rgtm1Sug/JicTac • 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. MODEL NUMBER 11503 TO ORDER 13 | Oncology US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] ONCOLOGY TACONIC BIOSCIENCES M O D E LS FO R SYNG ENEIC TU M O R E X P ERIMENTS WITH THE GROWTH IN IMMUNO-ONCOLOGY RESEARCH, SYNGENEIC MODELS ARE INCREASING IN POPULARITY. IN A SYNGENEIC TUMOR EXPERIMENT, A MOUSE TUMOR OR CELL LINE IS ENGRAFTED ONTO A WILD TYPE MOUSE OF THE SAME BACKGROUND STRAIN. AS THE HOST HAS A FULLY COMPETENT IMMUNE SYSTEM, THESE TYPES OF EXPERIMENTS ARE IDEAL FOR EVALUATION OF IMMUNO-ONCOLOGY THERAPEUTICS. C57BL/6 INBRED STRAIN • One of the most commonly used inbred strains for syngeneic tumor experiments, with a wide variety of C57BL/6-derived cell lines available. • May be used in combination with immunodeficients on C57BL/6 background (B6 nude, Rag2 knockout, Rag2/Il2rg (B10;B6)), with labeled strains (B6.SJL-Ptprca, OT-I or OT-II TCR transgenics), B6 albino, Diet Induced Obese Black 6 mice and many other GEM models. • Common cell lines: Breast (E0771), Colon (MC-38), Liver (Hep-55.1C), Lung (LLC1), Melanoma (B16, B16F10), Pancreas (Panc02), Prostate (Tramp-C1/2). • Available as SPF (Murine Pathogen Free™), SOPF (Excluded Flora) and as axenic (Germ Free). • Immunology: Th1-biased. MODEL NUMBER B6 N OMENCLATURE C57BL/6NTac MODEL NUMBER B6JBOM N OMENCLATURE C57BL/6JBomTac BALB/c INBRED STRAIN • One of the most commonly used inbred strains for syngeneic tumor experiments, with a wide variety of BALB/c-derived cell lines available. • May be used in combination with immunodeficients on BALB/c background (BALB/c nude, Rag2 knockout, CIEA BRG mouse). • Immunology: Th2-biased. MODEL NUMBER BALB • Common cell lines: Breast (4T1, MC4), Colon (CT26), Kidney (RenCa), Lymphoma (A20). • Available as SPF (Murine Pathogen Free™), SOPF (Excluded Flora) and as axenic (Germ Free). N OMENCLATURE BALB/cAnNTac MODEL NUMBER BALJBO N OMENCLATURE BALB/cJBomTac DISCUSS YOUR NEEDS US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Oncology | 14 ONCOLOGY TACONIC BIOSCIENCES C3H N OM EN CLATURE C3H/HeNTac INBRED STRAIN • General purpose strain, widely used in cancer research. • Immunology: Th1-biased. • Common cell lines: Bladder (MBT-2), Head and Neck (SCC-7), Lymphoma (38C13) Breast (CaD2). • Available as SOPF (Excluded Flora). MODEL NUMBER C3H DBA/2 N OM EN CLATURE DBA/2NTac INBRED STRAIN • General purpose strain, differs widely from C57BL/6 in many genetic loci. • Immunology: Th2-biased, Complement C5-deficient. • Common cell lines: Leukemia (L1210), Lung (KLN-205) Melanoma (Cloudman S91). • Available as SPF (Murine Pathogen Free™). MODEL NUMBER DBA2 TACONIC ALSO OFFERS THE DBA/1, SJL AND FVB STRAINS, WHICH ARE OCCASIONALLY USED IN SYNGENEIC TUMOR MODELS. Cancer and the microbiome Recent studies have identified a link between cancer and the microbiome, including differential response to immuno-oncology therapies. Taconic offers the most advanced portfolio of animal models and services for microbiome research, including: • Commercially available germ-free mice: C57BL/6, BALB/c, Swiss Webster • Germ-free derivations • Association of germ-free mice with client-provided microbiota • Range of available husbandry options for large or small study cohorts and short- or long-term animal studies including semi-rigid isolators and individually ventilated cages (IVCs) • Biospecimen collection • Shipment of conditioned animals or samples to client or CRO at study end Taconic shares its decades of experience in germ-free husbandry via educational support materials. Visit taconic.com/microbiome. TO ORDER 15 | Oncology US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] ONCOLOGY TACONIC BIOSCIENCES S PO NTANEO U S T UM OR MO DEL S Invasive Lobular Breast Cancer Model BREAST CANCER MODEL • Tissue-specific conditional knockout of Cdh1 (E-cadherin) and Trp53 in mice induces metastatic mammary carcinomas that resemble human invasive lobular carcinoma (ILC), the second most common type of primary breast cancer. • From the literature, it is estimated that females develop multiple skin and mammary tumors with a median latency of 214 days. N OMENCLATURE FVB.Cg-Cdh1tm1Jjon Trp53tm1Brn Tg(KRT14-cre)8Brn/A • Can be used to supply tumor tissues for allografts. • 20-30% of mice will develop nonmammary epithelial tumors. • This mouse model provides a valuable tool to gain insights into the role of E-cadherin loss of function in mammary tumor initiation, progression, and metastasis. MODEL NUMBER 11509 CRYOP RES ERVED Brca1-Associated Breast Cancer Model BREAST CANCER MODEL • Conditional mouse mutant with somatic deletion of Brca1 and Trp53 in several epithelial tissues including mammary epithelium. Female mice of this strain show a high incidence of mammary tumors that mimic many aspects of human BRCA1-mutated basal-like breast cancer. • Contains conditional disruption of the Trp53 tumor suppressor gene, the most commonly mutated gene in human cancers. • Contains conditional disruption of the Brca1 gene. Germline mutations of this gene are responsible for 40% to 50% of hereditary breast cancers. • This model may be helpful in predicting responses of human BRCA1-deficient tumors to therapies. N OMENCLATURE STOCK Trp53tm1Brn Brca1tm1Brn Tg(KRT14-cre)8Brn • Can be used to supply tumor tissues for allografts. • 20-30% of mice will develop nonmammary epithelial tumors. • From the literature, it is estimated that 80% of females develop multiple mammary and skin epithelial tumors with onset between 140 and 280 days. MODEL NUMBER 11510 CRYOP RES ERVED DISCUSS YOUR NEEDS US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Oncology | 16 ONCOLOGY TACONIC BIOSCIENCES Floxed Ink4a/Arf Mouse CONDITIONAL TUMOR SUPPRESSOR ALLELE • Contains a targeted mutation of Cdkn2a (Ink4a/Arf) which introduced LoxP sites upstream of exon 2 and downstream of exon 3. • Cross with the tissue-specific cre of your choice to develop a tumor model. N OM EN CLATURE B6.129P2-Cdkn2atm2Brn/A • The cell cycle inhibitory protein Cdkn2a is frequently disrupted in various types of human cancer, and germline mutations of this locus can confer susceptibility to melanoma and other tumors. • After deletion of the gene via crossing to a tissue-specific cre line, mice can develop tumors, giving rise to various sarcomas, carcinomas, lymphomas, and metastatic melanoma. MODEL NUMBER 11511 C RYO P RES ERV ED Floxed p53 Mouse N OM EN CLATURE CONDITIONAL TUMOR SUPPRESSOR ALLELE B6.129P2-Trp53tm1Brn/A • Contains a targeted mutation of Trp53 which introduced LoxP sites flanking exons 2 through 10. • Useful for studying Trp53 gene function or screening potential cancer intervention therapies. • Cross with the tissue-specific cre of your choice to generate a conditional disruption of the Trp53 tumor suppressor gene, the most commonly mutated gene in human cancers. • Conditional mutation avoids the predominance of non-epithelial tumors observed in constitutive Trp53 knockouts. • After deletion of the gene via crossing to a tissue-specific cre line, the incidence and the spectrum of tumors observed in homozygous or heterozygous mutant animals were comparable to those found in constitutive knockouts. MODEL NUMBER 11512 C RYO P RES ERV ED TO ORDER 17 | Oncology US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] ONCOLOGY TACONIC BIOSCIENCES S PO NTANE O U S T UM OR MO DEL S Pirc N OMENCLATURE COLON CANCER MODEL • Excellent model for study of human familial colon cancer. • ENU-induced point mutation results in a truncating mutation in the Apc gene at a site corresponding to the human mutation hotspot region of the gene. F344/NTac-Apcam1137 • Heterozygotes develop multiple tumors in the small intestine and colon by 2-4 months of age. • Pirc tumors closely resemble those in humans in terms of histopathology, morphology, and distribution between intestine and colon. • Longer lifespan compared to related mouse models (12-15 months). • Tumors may be visualized by CT, endoscopy or dissection. • Available for immediate cryorecovery. MODEL NUMBER PIRC CRYOP RES ERVED Stat 1 N OMENCLATURE MAMMARY TUMOR MODEL • Contains a homozygous disruption of the Stat1 gene and complete lack of functional STAT1 proteins. • The JAK-STAT signaling pathway has been implicated in mediating biologic responses induced by many cytokines. 129S6/SvEv-Stat1tm1Rds • Deficient immune cell response to alpha and gamma interferons. • Accelerated and amplified development of chemically-induced and spontaneous tumors. • Useful in unraveling the role of a variety of cytokines in immune responses, the role of STAT1 protein in mediating interferon-dependent responses, and the roles of tumor cells and immune cells in mediating tumor cell destruction. MODEL NUMBER 2045 DISCUSS YOUR NEEDS US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Oncology | 18 ONCOLOGY TACONIC BIOSCIENCES TSG-p53® N OM EN CLATURE TUMOR SUPPRESSOR KNOCK OUT • Contains a disruption of the Trp53 tumor suppressor gene, the most commonly mutated gene in human cancers. • Useful for studying Trp53 gene function or screening potential cancer intervention therapies. B6.129-Trp53tm1Brd N12 • Homozygous TSG-p53® mice are totally deficient in p53 protein and prone to the development of spontaneous tumors, primarily lymphomas and sarcomas. • Heterozygous TSG-p53® mice carry one normal p53 allele and have a much lower rate of spontaneous tumor development. MODEL NUMBER P53N12 C RYO P RES ERV ED TO ORDER 19 | Oncology US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] ONCOLOGY TACONIC BIOSCIENCES COMPARISON OF ONCOLOGY MOUSE AND RAT MODELS MODEL NUMBER MODEL NAME COAT COLOR T, B & NK CELL DEFICIENCIES BALBNU BALB/c nude mouse B6NU B6 nude mouse NCRNU NCr nude mouse NMRINU NMRI nude mouse NIHRNU NIH nude rat 9066* HRN™ nude mouse 1147 Jh CB17SC C.B-17 scid mouse ICRSC ICR scid mouse 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 4111 Rag2/Il2rg Double Knockout Mouse Dysfunctional antigen presenting cells (e.g. dendritic cells and macrophages). 11503 CIEA BRG mouse Dysfunctional antigen presenting cells (e.g. dendritic cells and macrophages). NOG CIEA NOG mouse® 13395 NOG-EXL (hGMCSF/hIL-3 NOG) 13440 hIL-2 NOG 13686 hIL-6 NOG 13683 hIL-15 NOG Shows reduced NK function OTHER IMMUNODEFICIENCIES Dysfunctional antigen presenting cells (e.g. dendritic cells and macrophages). Reduced complement activity, dysfunctional macrophages and dendritic cells. The most immune deficient mouse available. KEY: COAT COLOR CELL DEFICIENCIES Black and White Nude White-bellied agouti T Cell Deficient Black Nude Black B Cell Deficient Albino Nude Albino NK Cell Deficient * Lacks P450 activity in liver DISCUSS YOUR NEEDS US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Oncology | 20 ONCOLOGY TACONIC BIOSCIENCES INTEGRATED CUSTOM MODEL GENERATION CUSTOM MODEL GENERATION SOLUTIONS Taconic’s Genetically Engineered Models (GEMs) Design Solutions empower our clients to develop research models specifically suited to the unique discovery study needs or therapeutic programs. As a market leader with decades of experience in custom model generation, Taconic partners with clients to design, develop, and breed high quality genetically engineered mouse and rat models. GENE FUNCTION STUDIES GENE INACTIVATION DISEASE MODELING: MECHANISM OF PATHOGENESIS TRANSGENE EXPRESSION DISEASE MODELING: DRUG TESTING & DEVELOPMENT INDUCIBLE/ REVERSIBLE CONTROL OF GENE FUNCTION Constitutive knock out Targeted Transgenesis Conditional knock out Conditional Targeted Transgenesis Inducible/reversible RNA interference Conditional knock out with Cre-ER gene switch Random Transgenesis Inducible/reversible miRNA overexpression Constitutive with the option for conditional knock out GENE MUTATION OR REPLACEMENT Constitutive knock in Human gene knock in Human gene knock in with optional conditional knock out Conditional knock in Constitutive knock in point mutation with conditional knock out CRISPR Gene Editing TO ORDER 21 | Oncology US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] ONCOLOGY TACONIC BIOSCIENCES INTEGRATED CUSTOM BREEDING SOLUTIONS TACONIC OFFERS A SUITE OF PROJECT MANAGEMENT SERVICES TO HELP DRIVE NEW ONCOLOGY MODEL DEVELOPMENT FORWARD WITH INDUSTRY LEADING QUALITY AND SPEED. CUSTOM BREEDING SOLUTIONS Taconic’s fully integrated custom breeding solutions help bring novel oncology models from concept to study-ready cohorts with unprecedented speed and transparency. Customers can also combine Taconic’s portfolio of spontaneous and conditional tumor models with their existing or newly generated lines to delve into new frontiers. Our internal teams are led by PhDscientists trained in project management principles to balance speed, cost, and quality in order to meet your customized project goals. Custom Breeding Solutions coordinates flexible tools and advanced technologies, including: • Embryology Complete Portfolio and Project Management Access to Subject Matter Expertise • Animal housing • Molecular analysis • Surgery and specimen collection • Shipping animals with choice of animal identification system pre-applied Flexibility in Capabilities and Service Offerings Global E-Business Suite and Electronic Offerings DISCUSS YOUR NEEDS US: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Oncology | 22 ONCOLOGY Take Your Research Further GEMs DESIGN PRECISION RESEARCH MODELS GEMs MANAGEMENT Taconic Biosciences Genetically Engineered Models (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. 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. US: 1-888-822-6642 EU: +45 70 23 04 05 [email protected] TACONIC.COM ©Taconic Biosciences, Inc. All rights reserved. Contents of this publication may not be reproduced in any form without prior permission. BR1037-EN-1703 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] VISIT TACONIC.COM For more information on the entire Taconic portfolio of products and services designed to help further your research, visit taconic.com