Oncology Models and Services - Taconic Biosciences or scids, or for engraftment of patient-derived...

MODELS AND SERVICES DESIGNED

TO TAKE YOUR STUDY FURTHER

Oncology

TACONIC BIOSCIENCESONCOLOGY

TO ORDERUS: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] | Oncology

DISCUSS YOUR NEEDSUS: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Oncology | 3


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.

Evaluating the response of translational rodent models to new cancer therapies is the key to developing innovative treatment options.

Oncology

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.



HUMAN IMMUNE SYSTEM ENGRAFTED MODELS ...................................................................5

SUPER IMMUNODEFICIENT NOG MODELS ................................................................................8

IMMUNODEFICIENT MODELS ......................................................................................................... 12

Nudes...................................................................................................................................................... 12Scids ........................................................................................................................................................ 14Rag2 Models ........................................................................................................................................ 15

MODELS WITH MULTIPLE IMMUNODEFICIENCIES ............................................................... 16

MODELS FOR SYNGENEIC TUMOR EXPERIMENTS .............................................................. 17

SPONTANEOUS TUMOR MODELS ................................................................................................ 19

COMPARISON CHART OF ONCOLOGY MOUSE AND RAT MODELS ............................ 23

INTEGRATED CUSTOM MODEL GENERATION AND BREEDING SOLUTIONS .......... 24

TABLE OF CONTENTS


Oncology | 5DISCUSS YOUR NEEDSUS: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected]


TACONIC OFFERS

Human Immune System Engrafted ModelsImmunodeficient 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 immuno-oncology 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.

For additional information on these models,

visit taconic.com/his-mice

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

HOW CAN IMMUNE SYSTEM

ENGRAFTED NOG MICE BE USED?



• 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 patient-

derived PBMCs.

NOG MICE ENGRAFTED WITH HUMAN

PBMCs (PERIPHERAL BLOOD MONONUCLEAR CELLS)

• 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.

huNOGNOG MICE ENGRAFTED WITH HUMAN

CD34+ HEMATOPOIETIC STEM CELLS (HSCs)

huNOG-EXL

huPBMC-NOG

• 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.

NOG-EXL (HGM-CSF/HIL3-NOG) MICE ENGRAFTED WITH

HUMAN CD34+ HEMATOPOIETIC STEM CELLS (HSCs)

LICENSING: NO MTA OR LICENSE FEE IS REQUIRED FOR ANY OF THE MODELS FEATURED ON THIS PAGE.

huNOG-EXL MICE ARE AVAILABLE

OFF-THE-SHELF! PLACE YOUR ORDER

NOW FOR IMMEDIATE DELIVERY.

huNOG MICE ARE AVAILABLE

OFF-THE-SHELF! PLACE YOUR ORDER

NOW FOR IMMEDIATE DELIVERY.



COMMON MYELOIDPROGENITOR

IL-1IL-3GM-CSFSCF

COMMON LYMPHOIDPROGENITOR

IL-2IL-7IL-12SDF-1

IL-1 IL-6IL-2 IL-7IL-4

B LYMPHOCYTE TNK PROGENITOR

MYELOBLAST

GM-CSF

BASOPHIL

SCFG-CSFGM-CSFIL-3IL-6

NEUTROPHIL

SCFG-CSFGM-CSFIL-3IL-6

EOSINOPHIL

GM-CSFIL-3IL-5

MONOCYTE

SCFM-CSFG-CSFGM-CSFIL-3IL-6

huNOGhIL-2 NOG, hIL-15 NOGhIL-6 NOGhuNOG-EXL(hGM-CSF/hIL-3 NOG)

HEMATOPOIETICSTEM CELL

T LYMPHOCYTE

IL-2IL-7

NK CELL

IL-15IL-7

HEMATOPOIESIS AND HUMAN IMMUNE SYSTEM ENGRAFTED MICE

SUPER IMMUNODEFICIENT NOG MODELS



MODEL NUMBER NOG

NO MTA OR LICENSE FEE IS REQUIRED FOR PURCHASE.

MODEL NUMBER 13395

• 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, dysfunc-

tional macrophages and dendritic cells,

and deficiencies in immune signaling,

including impaired cytokine production.

• The polymorphism of SIRP-a allows the

mouse SIRP-a 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

hematopoietic stem cells (HSC).

• 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.

• 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.

• 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 SIRP-a allows the

mouse SIRP-a 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.


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.

CIEA NOG mouse®

NOG-EXL (hGM-CSF/hIL-3 NOG)

T, B & NK CELL DEFICIENT MOUSE WITH IMPAIRED

MYELOID FUNCTIONS; NOD BACKGROUND



NOD.Cg-Prkdcscid Il2rgtm1Sug/JicTac

NOD.Cg-Prkdcscid Il2rgtm1Sug Tg(SV40/HTLV-IL3,CSF2)10-7Jic/JicTac

NOMENCLATURE

NOMENCLATURE



• NOG mouse expressing human IL-2

cytokine.

• Predominant differentiation of human

NK cells following hHSC engraftment.


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.


cytokine.

• Enhanced expansion of human

monocytes following hHSC

engraftment.

• May be a suitable host for human IL-6

dependent tumor such as multiple

myeloma (MM) xenografts.


cytokine.

• Engraftment and expansion of human

NK cells following engraftment with

CD56+ NK cells derived from PBMC.

hIL-2 NOG

hIL-6 NOG

hIL-15 NOG







NOD.Cg-Prkdcscid Il2rgtm1Sug Tg(CMV-IL6)4-2Jic/JicTac

NOD.Cg-Prkdcscid Il2rgtm1Sug Tg(CMV-IL6)1-1Jic/JicTac

NOD.Cg-Prkdcscid Il2rgtm1Sug Tg(CMV-IL2/IL15)1-1Jic/JicTac

NOMENCLATURE

NOMENCLATURE

NOMENCLATURE

MODEL NUMBER 13440

MODEL NUMBER 13686

MODEL NUMBER 13683

LICENSING: NO MTA OR LICENSE FEE IS REQUIRED FOR ANY OF THE MODELS FEATURED ON THIS PAGE.



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HEMOLYTIC COMPLEMENT ACTIVITY – NOD scid AND NOG mice

Defect of hemolytic complement activity in sera of NOD scid and NOG mice.

The CIEA NOG mouse® shows defects in complement activity.

NK ACTIVITIES DEFECT – NOG mice

Defect of NK activities in spleen cells of NOG mice.

The CIEA NOG mouse® lacks NK cell activity.

NOGC.B-17 scid NOD scid

NOGC.B-17 scid NOD scid



CANCER ORIGIN

NUMBER OF IMPLANTED SAMPLES

NUMBER OF SUCCESSFUL PDX MODELS GENERATED

PRIMARY METASTATIC LYMPH NODE

PRIMARY METASTATIC LYMPH NODE

EPITHELIAL TISSUES

Large intestine 48 0 14 17 0 4

Stomach 18 3 2 3 1 1

Ampulla of Vater 4 0 0 2 0 0

Uterus 10 0 1 2 0 0

Ovary 18 2 0 1 1 0

Mammary gland 57 2 13 3 0 0

Cervix 4 0 2 0 0 1

Prostate 12 0 0 0 0 0

Testis 3 0 1 0 0 0

Kidney 18 0 0 3 0 0

Bladder 7 0 0 2 0 0

Lung 2 1 3 1 0 0

Pancreas 6 0 1 1 0 1

Skin 10 0 1 0 0 0

Thyroid 7 0 1 0 0 0

Others 4 1 3 0 0 0

Primary unknown 0 7 9 0 3 1

MESENCHYMAL TISSUES

Brain 6 0 0 1 0 0

Hematopoietic 6 0 0 0 0 0

Bone 3 0 0 0 0 0

Others 16 0 0 5 0 0

TOTALS 259 16 51 41 5 8

DEVELOPMENT OF PATIENT-DERIVED TUMOR LINES IN THE NOG MOUSEThe CIEA NOG mouse® may be used to establish patient-derived tumor models. Fresh human cancer samples were subcutaneously inoculated into the flank of NOG mice. A total of 326 tumor specimens were implanted into the mice, with in vivo tumor models successfully generated from 54 of the tumor samples (successfully passaged in vivo at least three times). Samples included tumor tissue from the original tumor site as well as metastatic sites and lymph nodes adjacent to the tumor. Histopathology of the derived in vivo tumor models was similar to that of the original tumor sample. Data from reference 1 and IWHM 2006 meeting (Poster 18): Chen YU et al., Tokyo, Japan, Oct 11-12, 2006.

CELL LINE CANCER CELL TYPE COMPARISON LINE

COMPARISON LINE TAKE RATE

NOG TAKE RATE

U2662,3 human multiple myeloma C.B-17 scid 0/5 20/20

U2662,3 human multiple myeloma NOD scid 0/5 20/20

A20584* human melanoma NOD scid 0/6 6/6

A3754* human melanoma NOD scid 0/9 8/9

G3614* human melanoma NOD scid 0/6 2/6

HMY-14* human melanoma NOD scid 0/8 2/8

AsPC-15** human pancreatic cancer NOD scid 8/9 9/9

BxPC-35** human pancreatic cancer NOD scid 0/8 8/8

Capan-15** human pancreatic cancer NOD scid 0/10 9/10

MIA PaCa-25** human pancreatic cancer NOD scid 0/10 10/10

PANC-15** human pancreatic cancer NOD scid 0/10 8/8

THE NOG MOUSE ENGRAFTS CELL LINES OTHER MODELS CANNOT

* Presence of distant metastases after iv inoculation.

** Measurement of liver metastases after intrasplenic injection.



• 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.

NCr nudeCrTac:NCr-Foxn1nu

IMMUNODEFICIENT MODELS

NUDESTHE 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.

• Foxn1nu mutation backcrossed to

the C57BL/6NTac inbred strain for

ten generations.

B6 nudeT CELL DEFICIENT MOUSE

MODEL NUMBER B6NU

B6.Cg/NTac-Foxn1nu NE10

• Foxn1nu mutation backcrossed to

the BALB/cAnN inbred strain for

nine generations.

BALB/c nudeC.Cg/AnNTac-Foxn1nu NE9

NOMENCLATURE

NOMENCLATURE

T CELL DEFICIENT MOUSE

MODEL NUMBER BALBNU

NOMENCLATURE


MODEL NUMBER NCRNU



NTac:NIH-Foxn1rnu

• 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.

NIH nudeT CELL DEFICIENT RAT

NOMENCLATURE

MODEL NUMBER NIHRNU

• 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.

• 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.

NMRI nudeT CELL DEFICIENT MOUSE

HRN™ nude

BomTac:NMRI-Foxn1nu

CrTac:NCr-Portm1Wolf Foxn1nu Tg(Alb-cre)21Mgn

NOMENCLATURE

MODEL NUMBER NMRINU

NOMENCLATURE

CRYOPRESERVED


MODEL NUMBER 9066



SCIDs SEVERE COMBINED IMMUNODEFICIENCY

MICE HOMOZYGOUS FOR THE Prkdcscid 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).

• 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).

ICR scidT & B CELL DEFICIENT MOUSE IcrTac:ICR-Prkdcscid

• The scid mutation has been transferred

onto a diabetes-susceptible Non-Obese

Diabetic (NOD).

• 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.

NOD scidNOD/MrkBomTac-Prkdcscid

• 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™.

C.B-17 scidT & B CELL DEFICIENT MOUSE C.B-Igh-1b/IcrTac-Prkdcscid

NOMENCLATURE

MODEL NUMBER CB17SC

NOMENCLATURE

MODEL NUMBER ICRSC

NOMENCLATURE

T & B CELL DEFICIENT MOUSE

MODEL NUMBER NODSC



Rag2 MODELSMICE 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.

• The 129S6 strain was the original strain in which the

Rag2 targeted mutation was created.

Rag2 (129S6)129S6/SvEvTac-Rag2tm1Fwa

NOMENCLATURE


MODEL NUMBER RAG2

• Backcrossed twelve generations (N12) to the

BALB/cAnNTac inbred strain.

Rag2 (BALB/c)C.129S6(B6)-Rag2tm1Fwa N12

NOMENCLATURE


MODEL NUMBER 601

• Similar to C57BL/6 with the H2b haplotype, but carries

the Ptprca and Pep3b genes from the SJL strain (CD45.1).

Rag2 (B6.SJL)B6.SJL(129S6)-Ptprca/BoyCrTac Rag2tm1Fwa N10

NOMENCLATURE


MODEL NUMBER 461

• Backcrossed twelve generations (N12) to the

C57BL/6NTac inbred strain.

Rag2 (C57BL/6)B6.129S6-Rag2tm1Fwa N12

NOMENCLATURE


MODEL NUMBER RAGN12

CRYOPRESERVED

CRYOPRESERVED



MODELS WITH MULTIPLE IMMUNODEFICIENCIES

• 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.

CIEA BRG mouseT, B & NK CELL DEFICIENT C.Cg-Rag2tm1Fwa Il2rgtm1Sug/JicTac

Rag2/Il2rg Double Knockout MouseT, B & NK CELL DEFICIENT MOUSE

B10;B6-Rag2tm1Fwa Il2rgtm1Wjl

• 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.

• 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.

• It also carries the beige mutation

which results in cytotoxic T cell

and macrophage defects as well

as selective impairment of

NK cell functions.

Scid-beigeT, B & NK CELL DEFICIENT MOUSE C.B-Igh-1b/GbmsTac-Prkdcscid Lystbg N7

NOMENCLATURE

MODEL NUMBER CBSCBG

NOMENCLATURE

NOMENCLATURE

MODEL NUMBER 4111

MODEL NUMBER 11503



MODELS FOR SYNGENEIC TUMOR EXPERIMENTS

• One of the most commonly used

inbred strains for syngeneic tumor

experiments, with a wide variety of

C57BL/6-derived cell lines available.


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.

• Immunology: Th1-biased.

• 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).

• One of the most commonly used

inbred strains for syngeneic tumor

experiments, with a wide variety of

BALB/c-derived cell lines available.


immunodeficients on BALB/c

background (BALB/c nude, Rag2

knockout, CIEA BRG mouse).


• 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).

C57BL/6

BALB/c

INBRED STRAIN

INBRED STRAIN

C57BL/6NTac

BALB/cAnNTac

C57BL/6JBomTac

BALB/cJBomTac

NOMENCLATURE

NOMENCLATURE

NOMENCLATURE

NOMENCLATURE

MODEL NUMBER B6

MODEL NUMBER BALB

MODEL NUMBER B6JBOM

MODEL NUMBER BALJBO

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.



• General purpose strain, widely used in

cancer research.


• Common cell lines: Bladder (MBT-2),

Head and Neck (SCC-7), Lymphoma

(38C13) Breast (CaD2).

• Available as SOPF (Excluded Flora).

• 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™).

C3H

DBA/2

INBRED STRAIN

INBRED STRAIN

C3H/HeNTac

DBA/2NTac

NOMENCLATURE

NOMENCLATURE

MODEL NUMBER C3H

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.




SPONTANEOUS TUMOR MODELS

• 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.

• 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.

• Can be used to supply tumor tissues

for allografts.

• 20-30% of mice will develop non-

mammary epithelial tumors.

Invasive Lobular Breast Cancer ModelBREAST CANCER MODEL

FVB.Cg-Cdh1tm1Jjon Trp53tm1Brn Tg(KRT14-cre)8Brn/A

NOMENCLATURE

MODEL NUMBER 11509

• 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

Brca1 gene. Germline mutations of this

gene are responsible for 40% to 50% of

hereditary breast cancers.

• Contains conditional disruption of

the Trp53 tumor suppressor gene,

the most commonly mutated gene

in human cancers.

• From the literature, it is estimated

that 80% of females develop multiple

mammary and skin epithelial tumors

with onset between 140 and 280 days.

• This model may be helpful in predicting

responses of human BRCA1-deficient

tumors to therapies.

• Can be used to supply tumor tissues

for allografts.

• 20-30% of mice will develop non-

mammary epithelial tumors.

Brca1-Associated Breast Cancer ModelBREAST CANCER MODEL

STOCK Trp53tm1Brn Brca1tm1Brn Tg(KRT14-cre)8Brn

NOMENCLATURE

MODEL NUMBER 11510

CRYOPRESERVED

CRYOPRESERVED




Floxed p53 MouseCONDITIONAL TUMOR SUPPRESSOR ALLELE B6.129P2-Trp53tm1Brn/A

• Contains a targeted mutation of Trp53

which introduced LoxP sites flanking

exons 2 through 10.

• 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.

• Useful for studying Trp53 gene

function or screening potential cancer

intervention therapies.

• 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.

• 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.

• 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.

Floxed Ink4a/Arf MouseCONDITIONAL TUMOR SUPPRESSOR ALLELE B6.129P2-Cdkn2atm2Brn/A

NOMENCLATURE

MODEL NUMBER 11511

NOMENCLATURE

MODEL NUMBER 11512

CRYOPRESERVED

CRYOPRESERVED




• 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.

• 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.

PircCOLON CANCER MODEL F344/NTac-Apcam1137

NOMENCLATURE

MODEL NUMBER PIRC

• 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.

• 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.

Stat 1MAMMARY TUMOR MODEL 129S6/SvEv-Stat1tm1Rds

NOMENCLATURE

MODEL NUMBER 2045

CRYOPRESERVED




• 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.

• 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.

TSG-p53®

TUMOR SUPPRESSOR KNOCKOUT B6.129-Trp53tm1Brd N12

NOMENCLATURE

MODEL NUMBER P53N12

CRYOPRESERVED



MODEL NUMBER MODEL NAME COAT COLOR T, B & NK CELL DEFICIENCIES OTHER IMMUNODEFICIENCIES

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 Shows reduced NK function

Dysfunctional antigen presenting cells (e.g. dendritic cells and macrophages).

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®

Reduced complement activity, dysfunctional macrophages and dendritic cells. The most immune deficient mouse available.

13395 NOG-EXL (hGM-CSF/hIL-3 NOG)

13440 hIL-2 NOG

13686 hIL-6 NOG

13683 hIL-15 NOG

COMPARISON OF ONCOLOGY MOUSE AND RAT MODELS

COAT COLOR CELL DEFICIENCIES

T Cell Deficient

B Cell Deficient

NK Cell DeficientAlbino

Black

Black and White Nude

Albino Nude

Black Nude

White-bellied agouti

KEY:

* Lacks P450 activity in liver



Constitutive knockout

Conditional knockout

Conditional knockout with Cre-ER gene switch

Constitutive with the option for conditional knockout

GENE FUNCTION STUDIES DISEASE MODELING: MECHANISM OF PATHOGENESIS

DISEASE MODELING:DRUG TESTING & DEVELOPMENT

Targeted Transgenesis

Conditional Targeted Transgenesis

Random Transgenesis

Inducible/reversible RNA interference

Inducible/reversible miRNA overexpression

TRANSGENE EXPRESSION

GENEINACTIVATION

INDUCIBLE/ REVERSIBLE CONTROL OF GENE FUNCTION

Constitutive knock-in

Human gene knock-in

Human gene knock-in with optional conditional knockout

Conditional knock-in

Constitutive knock-in point mutation with conditional knockout

CRISPR Gene Editing

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 MUTATION OR REPLACEMENT

INTEGRATED CUSTOM MODEL GENERATION



TACONIC OFFERS A SUITE OF PROJECT MANAGEMENT SERVICES

TO HELP DRIVE NEW ONCOLOGY MODEL DEVELOPMENT

FORWARD WITH INDUSTRY LEADING QUALITY AND SPEED.

Complete Portfolio and Project Management

Access to Subject Matter Expertise

Flexibility inCapabilities and Service Offerings

Global E-Business Suite and Electronic Offerings

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 PhD-

scientists 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

• Animal housing

• Molecular analysis

• Surgery and specimen collection

• Shipping animals with choice of animal identification system pre-applied

INTEGRATED CUSTOM BREEDING SOLUTIONS



1. Fujii E, Suzuki M, Matsubara K, Watanabe M, Chen YJ, Adachi K, Ohnishi Y, Tanigawa M, Tsuchiya M, Tamaoki N. (2008)

Establishment and characterization of in vivo human tumor models in the NOD/SCID/gamma(c)(null) mouse. Pathol Int

58(9):559-67.

2. Miyakawa Y, Ohnishi Y, Tomisawa M, Monnai M, Kohmura K, Ueyama Y, Ito M, Ikeda Y, Kizaki M, Nakamura M. (2004)

Establishment of a new model of human multiple myeloma using NOD/SCID/gammacnull (NOG) mice. Biochem Biophys

Res Commun., 313:258-262.

3. Dewan Z, Watanabe M, Terashima K, Aoki M, Sata T, Honda M, Ito M, Yamaoka S, Watanabe T, Horie R, Yamamoto N.

(2004) Prompt tumor formation and maintenance of constitutive NF-kB activity of multiple myeloma cells in NOD/SCID/

gammacnull mice. Cancer Sci., 95(7):564-568.

4. Ikoma N, Yamazaki H, Abe Y, Oida Y, Ohnishi Y, Suemizu H, Matsumoto H, Matsuyama T, Ohta Y, Ozawa A, Ueyama Y,

Nakamura M. (2005) S100A4 expression with reduced E-cadherin expression predicts distant metastasis of human

malignant melanoma cell lines in the NOD/SCID/gammacnull (NOG) mouse model. Oncol Rep., 14:633-637.

5. Suemizu H, Monnai M, Ohnishi Y, Ito M, Tamaoki N, Nakamura M. (2007) Identification of a key molecular regulator of liver

metastasis in human pancreatic carcinoma using a novel new quantitative model of metastasis in NOD/SCID/gammacnull

(NOG) mice. Int J Oncol., 31(4):741-51.

REFERENCES FOR CIEA NOG mouse®

ON PAGE 11

CHOOSE TACONIC

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.

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.

TALK TO A SCIENTIST

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.

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

Take Your Research Further

GEMs MANAGEMENT

Taconic’s fully integrated GEMs

Management brings innovative models

from design to study-ready cohorts with

unprecedented speed and transparency.

• Embryology

• Rapid Colony Expansion

• Contract Breeding

• Surgical Services

• Tissue Collection

• Genotyping and Molecular Analysis

• Microbiome and Germ-Free Research

Models and Services

GEMs DESIGN

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.

• Gene Inactivation

• Gene Mutation or Replacement

• CRISPR Gene Editing

• Transgene Expression

• miRNA Expression

• Cohort Production Packages

PRECISION RESEARCH MODELS

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.

• Human Gene Replacement

• Human Cell and Tissue Engraftment

©Taconic Biosciences, Inc. All rights reserved. Contents of this publication

may not be reproduced in any form without prior permission.

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