oncology models and services - taconic biosciences...nudes or scids, or for engraftment of...
TRANSCRIPT
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 BIOSCIENCESONCOLOGY
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.
TACONIC BIOSCIENCESONCOLOGY
TO ORDERUS: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] | Oncology
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
TACONIC BIOSCIENCESONCOLOGY
Oncology | 5DISCUSS YOUR NEEDSUS: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected]
TACONIC BIOSCIENCESONCOLOGY
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?
TACONIC BIOSCIENCESONCOLOGY
TO ORDERUS: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] | Oncology
• 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.
TACONIC BIOSCIENCESONCOLOGY
DISCUSS YOUR NEEDSUS: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Oncology | 7
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
TO ORDERUS: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] | Oncology
TACONIC BIOSCIENCESONCOLOGY
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.
• 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.
CIEA NOG mouse®
NOG-EXL (hGM-CSF/hIL-3 NOG)
T, B & NK CELL DEFICIENT MOUSE WITH IMPAIRED
MYELOID FUNCTIONS; NOD BACKGROUND
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
DISCUSS YOUR NEEDSUS: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Oncology | 9
TACONIC BIOSCIENCESONCOLOGY
• NOG mouse expressing human IL-2
cytokine.
• Predominant differentiation of human
NK cells following hHSC engraftment.
• 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.
• NOG mouse expressing human IL-6
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.
• NOG mouse expressing human IL-15
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
T, B & NK CELL DEFICIENT MOUSE WITH IMPAIRED
MYELOID FUNCTIONS; NOD BACKGROUND
T, B & NK CELL DEFICIENT MOUSE WITH IMPAIRED
MYELOID FUNCTIONS; NOD BACKGROUND
T, B & NK CELL DEFICIENT MOUSE WITH IMPAIRED
MYELOID FUNCTIONS; NOD BACKGROUND
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.
TACONIC BIOSCIENCESONCOLOGY
TO ORDERUS: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] | Oncology
%
SP
EC
IFIC
RE
LE
AS
E
SERUM DILUTION
0
20
40
60
80
100
1/641/321/161/81/41/2
0
20
40
60
80
100
1/641/321/161/81/41/2
%
CY
TO
TO
XIC
ITY
E:T RATIO
0
20
40
60
80
100
100:1100:133:1100:1
0
20
40
60
80
100
100:1100:133:1100:1
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
TACONIC BIOSCIENCESONCOLOGY
DISCUSS YOUR NEEDSUS: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Oncology | 11
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.
TO ORDERUS: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] | Oncology
TACONIC BIOSCIENCESONCOLOGY
• 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
T CELL DEFICIENT MOUSE
MODEL NUMBER NCRNU
TACONIC BIOSCIENCESONCOLOGY
DISCUSS YOUR NEEDSUS: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Oncology | 13
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
T CELL DEFICIENT MOUSE
MODEL NUMBER 9066
TO ORDERUS: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] | Oncology
TACONIC BIOSCIENCESONCOLOGY
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
DISCUSS YOUR NEEDSUS: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Oncology | 15
TACONIC BIOSCIENCESONCOLOGY
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
T & B CELL DEFICIENT MOUSE
MODEL NUMBER RAG2
• Backcrossed twelve generations (N12) to the
BALB/cAnNTac inbred strain.
Rag2 (BALB/c)C.129S6(B6)-Rag2tm1Fwa N12
NOMENCLATURE
T & B CELL DEFICIENT MOUSE
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
T & B CELL DEFICIENT MOUSE
MODEL NUMBER 461
• Backcrossed twelve generations (N12) to the
C57BL/6NTac inbred strain.
Rag2 (C57BL/6)B6.129S6-Rag2tm1Fwa N12
NOMENCLATURE
T & B CELL DEFICIENT MOUSE
MODEL NUMBER RAGN12
CRYOPRESERVED
CRYOPRESERVED
TO ORDERUS: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] | Oncology
TACONIC BIOSCIENCESONCOLOGY
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
DISCUSS YOUR NEEDSUS: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Oncology | 17
TACONIC BIOSCIENCESONCOLOGY
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.
• 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.
• 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.
• May be used in combination with
immunodeficients on BALB/c
background (BALB/c nude, Rag2
knockout, CIEA BRG mouse).
• Immunology: Th2-biased.
• 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.
TO ORDERUS: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] | Oncology
TACONIC BIOSCIENCESONCOLOGY
• 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).
• 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.
DISCUSS YOUR NEEDSUS: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Oncology | 19
TACONIC BIOSCIENCESONCOLOGY
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
TO ORDERUS: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] | Oncology
TACONIC BIOSCIENCESONCOLOGY
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
DISCUSS YOUR NEEDSUS: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Oncology | 21
TACONIC BIOSCIENCESONCOLOGY
• 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
TO ORDERUS: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] | Oncology
TACONIC BIOSCIENCESONCOLOGY
• 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
TACONIC BIOSCIENCESONCOLOGY
DISCUSS YOUR NEEDSUS: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Oncology | 23
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
TO ORDERUS: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] | Oncology
TACONIC BIOSCIENCESONCOLOGY
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
DISCUSS YOUR NEEDSUS: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] Oncology | 25
TACONIC BIOSCIENCESONCOLOGY
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
TACONIC BIOSCIENCESONCOLOGY
TO ORDERUS: 1-888-822-6642 | EU: +45 70 23 04 05 | [email protected] | Oncology
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.
US: 1-888-822-6642
EU: +45 70 23 04 05
TACONIC.COM
BR1037-EN-1705
ONCOLOGY