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MODELS AND SERVICES DESIGNED TO TAKE YOUR STUDY FURTHER Metabolic and Cardiovascular Disease Models and Services

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Page 1: Metabolic and Cardiovascular Disease Models and Services · Metabolic and Cardiovascular Disease Models ... models such as the off-the-shelf diet- ... Metabolic and Cardiovascular

MODELS AND SERVICES DESIGNED

TO TAKE YOUR STUDY FURTHER

Metabolic and Cardiovascular

Disease Models and Services

Page 2: Metabolic and Cardiovascular Disease Models and Services · Metabolic and Cardiovascular Disease Models ... models such as the off-the-shelf diet- ... Metabolic and Cardiovascular

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

TACONIC BIOSCIENCESMETABOLIC AND CARDIOVASCULAR DISEASE

Metabolic and Cardiovascular Disease

The availability of predictive animal models is essential for the advancement of this vital research. To address this need, Taconic Biosciences offers a wide range of models and services including traditional and spontaneous mutants, transgenic models, and study-ready models such as the off-the-shelf diet-induced obesity model (DIO).

Diabetes, hypertension, heart disease and obesity have reached epidemic proportions, making research into cardiovascular and metabolic disorders a top priority.

Metabolic and Cardiovascular Disease Models and Services

Over 300 million people

suffer from diabetes.

Taconic assists researchers

with models that mimic

human disease for the study

of different aspects

of metabolic and

cardiovascular disease.

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TACONIC BIOSCIENCESMETABOLIC AND CARDIOVASCULAR DISEASE

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

TTMTACONIC TRANSGENIC MODELS™

Taconic Transgenic Models™ (TTMs™) are important research models offered off-the-shelf in typical study quantities. TTMs™ carry a label license granting you the intellectual property right(s) to use the model in your research.

Page 4: Metabolic and Cardiovascular Disease Models and Services · Metabolic and Cardiovascular Disease Models ... models such as the off-the-shelf diet- ... Metabolic and Cardiovascular

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

TACONIC BIOSCIENCESMETABOLIC AND CARDIOVASCULAR DISEASE

Metabolic and Cardiovascular Disease

• Contains a disruption of the

endogenous murine apolipoprotein

E gene.

• Homozygous ApoE mice are devoid

of apoE protein.

• Mice develop normally, but exhibit five

times normal serum plasma cholesterol

and spontaneous atherosclerotic

lesions when maintained on a

standard diet.

ApoeCARDIOVASCULAR DISEASE MODEL

CONSTITUTIVE KNOCKOUT MOUSE

C57BL/6 BACKGROUND

MODEL NUMBER APOE

B6.129P2-Apoetm1Unc N11

NOMENCLATURE

• Homozygous for a human APOE*2

gene through targeted replacement of

the endogenous mouse Apoe gene.

• Expresses human apolipoprotein E2

isoform under the control of the murine

Apoe regulatory sequences.

• Develops hyperlipoproteinemia with

elevated plasma cholesterol and

triglyceride levels, decreased clearance

of vLDL particles, and spontaneous

atherosclerotic plaques on a normal

diet, exacerbated by a high fat diet.

APOE2CARDIOVASCULAR DISEASE MODEL

TARGETED REPLACEMENT

C57BL/6 BACKGROUND

MODEL NUMBER 1547

B6.129P2-Apoetm1(APOE*2)Mae N9

NOMENCLATURE

• Homozygous for a human APOE*3

gene through targeted replacement of

the endogenous mouse Apoe gene.

• Expresses human apolipoprotein E3

isoform under the control of the murine

Apoe regulatory sequences.

• Exhibits an increased risk of atheroscle-

rosis and hypercholesterolemia

compared with wild type mice on a

high fat diet, but not on a normal diet.

• Useful for studying the role of human

APOE3, which is the most commo form

of human APOE in diseases related to

APOE isoforms.

APOE3CARDIOVASCULAR DISEASE MODEL

TARGETED REPLACEMENT

C57BL/6 BACKGROUND

MODEL NUMBER 1548

B6.129P2-Apoetm2(APOE*3)Mae N8

NOMENCLATURE

Page 5: Metabolic and Cardiovascular Disease Models and Services · Metabolic and Cardiovascular Disease Models ... models such as the off-the-shelf diet- ... Metabolic and Cardiovascular

TACONIC BIOSCIENCESMETABOLIC AND CARDIOVASCULAR DISEASE

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

• Homozygous for a human APOE*4

gene through targeted replacement

of endogenous mouse Apoe gene.

• Expresses human apolipoprotein E4

isoform under the control of the

murine Apoe regulatory sequences.

• Exhibits an increased risk of

atherosclerosis compared with

wild type and APOE3 targeted

replacement mice.

• Useful for studying the role of human

APOE polymorphism in atherosclerosis

and lipid metabolism.

• On a high-fat diet, develops abnormal

serum lipid profiles and atherosclerotic

plaques that are more severe than the

APOE3 model, with twice the choles-

terol, ApoE, and ApoB-48 levels and

larger plaques than the APOE3 model.

• Contains the human apolipoprotein

B transgene.

• ApoB100 is the predominant human

ApoB species found in plasma of

ApoB100 mice.

• ApoB100 mice show elevated serum

levels of LDL cholesterol.

• Develops atherosclerosis on a high

fat, high cholesterol diet.

• Useful for identifying and evaluating

compounds to reduce LDL levels and

the risk of atherosclerosis.

• Also useful for studies of lipid transport

and atherosclerosis.

APOE4CARDIOVASCULAR DISEASE MODEL

TARGETED REPLACEMENT

C57BL/6 BACKGROUND

MODEL NUMBER 1549

B6.129P2-Apoetm3(APOE*4)Mae N8

NOMENCLATURE

ApoB100CARDIOVASCULAR DISEASE MODEL

RANDOM TRANGENIC

C57BL/6 BACKGROUND

MODEL NUMBER 1004

B6.SJL-Tg(APOB)1102Sgy N20+?

NOMENCLATURE

CETP-ApoB100CARDIOVASCULAR DISEASE MODEL

RANDOM TRANGENIC

C57BL/6 BACKGROUND

MODEL NUMBER 3716

B6.SJL-Tg(APOA-CETP)1Dsg Tg(APOB)1102Sgy N10

NOMENCLATURE

• Carries both human cholesteryl

ester transfer protein and human

apolipoprotein B transgenes.

• Exhibits human-like serum

HDL/LDL distribution.

• When fed a high fat, high cholesterol

diet this mouse develops complex

atherosclerotic lesions.

• Useful for evaluating compounds to

treat hypercholesterolemia or HDL/

LDL imbalance to reduce the risk of

developing atherosclerosis.

Page 6: Metabolic and Cardiovascular Disease Models and Services · Metabolic and Cardiovascular Disease Models ... models such as the off-the-shelf diet- ... Metabolic and Cardiovascular

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

TACONIC BIOSCIENCESMETABOLIC AND CARDIOVASCULAR DISEASE

Metabolic and Cardiovascular Disease

CARDIOVASCULAR AND METABOLIC DISEASE MODEL

CONSTITUTIVE KNOCK OUT MOUSE

C57BL/6 BACKGROUND

• Contains human cholesteryl ester

transfer protein transgene.

• Exhibits dramatic reduction

in serum HDL cholesterol.

• Useful for identifying and evaluating

compounds that increase HDL levels.

• Serves as one control for the CETP-

ApoB100 mouse model.

• Contains a disruption of the Ppara

(peroxisome proliferator activated

receptor α) gene.

• No profound hepatomegaly,

peroxisomal proliferation or

induction of fatty acid oxidation

enzymes in response to classical

peroxisome proliferators.

• Higher serum cholesterol

and apoA-I concentrations

than wild type controls.

• Altered fatty acid metabolism

including lower β-oxidation of

palmitic acid.

• β-oxidation of very long chain fatty

acids is not altered.

• Useful in the study of lipid and glucose

homeostasis, fatty acid metabolism

and as a potential model for inborn

errors of metabolism.

CETPCARDIOVASCULAR DISEASE MODEL

RANDOM TRANGENIC

C57BL/6 BACKGROUND

MODEL NUMBER 3715

B6.SJL-Tg(APOA-CETP)1Dsg N11

NOMENCLATURE

Pparα

MODEL NUMBER 1640

B6.129S4-Pparatm1Gonz N12

NOMENCLATURE

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TACONIC BIOSCIENCESMETABOLIC AND CARDIOVASCULAR DISEASE

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

LIGHT PRODUCINGTRANSGENIC ANIMALS® (LPTA®)

Reporter models expressing luciferase under the control of various promoters, for use in bioluminescent imaging both in vivo and ex vivo.

Each mouse or rat model

varies in the promoter used

to control the luciferase

reporter gene.

EMERGING MODELS

RIP-lucUseful for the study of transcriptional

regulation of the insulin promoter,

changes in insulin production (resulting

from fasting, streptozotocin treatment

etc.), and for pancreatic islet

transplantation studies.

LPTA® models relevant to the study of metabolic and cardiovascular disorders include:

Retn-luc Useful for obesity studies (including

fasting, high-fat feeding, insulin

resistance), and for adipose tissue

transplantation studies.

mlns2-lucUseful for the study of changes in insulin

production (resulting from fasting,

high-fat diet feeding, streptozotocin

treatment etc.), and for pancreatic islet

transplantation studies.

In this model, the mouse insulin promoter

drives the expression of luciferase.

Visit Taconic.com/lpta for a listing

of all available LPTA® models.

* LPTA models are made available from Taconic under a license from Caliper Life Sciences and Promega Corporation. Other third party rights may apply. Refer to Taconic.com/lpta for the LPTA® Conditions of Use.

Page 8: Metabolic and Cardiovascular Disease Models and Services · Metabolic and Cardiovascular Disease Models ... models such as the off-the-shelf diet- ... Metabolic and Cardiovascular

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

TACONIC BIOSCIENCESMETABOLIC AND CARDIOVASCULAR DISEASE

Metabolic and Cardiovascular Disease

NOD/MrkTac

• A non-obese model of Non-Insulin

Dependent Diabetes Mellitus (NIDDM),

type 2 diabetes.

• Exhibits similar metabolic, hormonal

and vascular disorders to the human

diabetes disease

• Males typically develop type 2 diabetes

at 14-16 weeks of age.

• Characteristics include fasting

hyperglycemia, impaired secretion

of insulin in response to glucose and

polyuria and hepatic and peripheral

insulin resistance.

• Late complications such as retinopathy,

microangiopathy, neuropathy and

nephropathy have been reported in

the literature.

• Diet does play a role in onset and

severity of phenotype development.

Goto-Kakizaki RatDIABETES MODEL

INBRED RAT

GK/MolTac

NOMENCLATURE

MODEL NUMBER GK

• Exhibits destructive autoimmune

pancreatic insulitis as early as four

weeks of age.

• Insulin-Dependent Diabetes Melitus

(IDDM), type 1 diabetes, is found in

some females beginning at three

months of age and in approximately

80% of females and 50% of males

by six months of age.

Non-Obese Diabetic MouseDIABETES MODEL

INBRED MOUSE

NOMENCLATURE

MODEL NUMBER NOD

TRADITIONAL MODELS

• The most widely used inbred strain for

diet induced obesity research due to

susceptibility to high fat diet.

• Popular in research applications of

oncology, immunology, toxicology.

• Now available at the Germ-Free health

profile in addition to Excluded Flora,

Restricted FloraTM and Murine Pathogen

FreeTM health profiles.

• Taconic’s B6 sublines do not carry the

known Nnt mutation.

Black 6AGING/DIET INDUCED OBESE MODEL

INBRED MOUSE

MODEL NUMBER B6

C57BL/6NTac

NOMENCLATURE

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TACONIC BIOSCIENCESMETABOLIC AND CARDIOVASCULAR DISEASE

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

• Males exhibit average systolic blood

pressure greater than 200 mm Hg

by 3-4 months of age.

• Generally used for studies in

hypertension and cardiovascular

research.

• A suitable model for the study of

diabetic neuropathology

and nephropathy.

• Also used in the study of the

pathogenesis and prevention of

Type 2 Non-Insulin Dependent

Diabetes Mellitus (NIDDM).

• Experiences a hyperinsulinemic phase

(Phase 1) followed by a hypoinsulinemic

phase (Phase 2) at 2–3 months of age.

• Due to possible crossover of the misty

(m) and Leprdb genes, a low percentage

of DB-M could be heterozygous for the

misty (m) gene.

• Only homozygotes are diabetic and

obese, heterozygotes and wild types

are non-diabetic and lean

DiabeticDIABETES/OBESITY MODEL

SPONTANEOUS MUTANT MOUSE

BKS BACKGROUND

BKS.Cg-m+/+Leprdb/BomTac

NOMENCLATURE

MODEL NUMBER DB

MODEL NUMBER SHR

Spontaneously Hypertensive RatHYPERTENSION/CONGESTIVE HEART FAILURE DISEASE MODEL

OUTBRED RAT

NTac:SHR

NOMENCLATURE

SPONTANEOUS MUTANT MODEL

Page 10: Metabolic and Cardiovascular Disease Models and Services · Metabolic and Cardiovascular Disease Models ... models such as the off-the-shelf diet- ... Metabolic and Cardiovascular

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

TACONIC BIOSCIENCESMETABOLIC AND CARDIOVASCULAR DISEASE

Metabolic and Cardiovascular Disease

MODEL NUMBER DIO-B6

• Taconic maintains an inventory of

C57BL/6NTac male mice on 60%

fat kcal irradiated diet. Taconic uses

Research Diets industry standard high

fat rodent diet, D12492. Control mice

at the same age on the NIH-31M diet

are also available.

• Mice are placed on an irradiated,

sterility tested, high fat diet

(RDI#12492) at 6 weeks of age.

• RDI D12492 is a 35% high fat and high

carbohydrate diet. It is 35% fat by

weight and 60% fat by kcal.

• Animals are maintained on diet up

to 21 weeks of age.

• These mice exhibit similar metabolic,

hormonal and vascular disorders to

the human diabetes disease.

• Characteristics include fasting hyper-

glycemia, impaired secretion of insulin

in response to glucose both in vivo

and in isolated pancreatic cells,

hepatic and peripheral insulin

resistance and polyuria.

Diet Induced Obese DIO-B6 MouseOBESITY MODEL

C57BL/6NTac

NOMENCLATURE

STUDY-READY MODEL

TESTING SOLUTIONS

MOLECULAR ANALYSIS SERVICES

Pre-validated genotyping assays

Taconic offers a variety of pre-validated genotyping assays

to complement our portfolio of metabolic disease models.

For example, the Obese spontaneous mutant mouse must be

homozygous for the Lepob allele to exhibit the obese phenotype.

Taconic has a functional pyrosequencing assay that can screen

for Lepob homozygotes as well as genotyping assays for all

Taconic Transgenic Models™ mentioned in this booklet.

Taconic uses both classic- and high- throughput,

real-time PCR methods for genotyping.

Our comprehensive approach ensures our

clients receive the best service in the industry.

Advantages of pre-validated assays:

• No initial set-up costs for assay development

• No time-lag for new assay development

• Great cost savings when genotyping multiple

alleles using Taconic’s real-time platform

• Spend more time on your research and less

time genotyping

STUDY-READY OPTIONS

BLOOD COLLECTION AND TISSUE HARVESTING

Baseline, interim, and terminal (via cardiac puncture)

blood samples can be collected and shipped to the client.

Taconic’s expert staff have broad experiences with tissue

dissections, and collections for a variety of purposes.

Taconic also offers tissue RNA extraction which is

performed with our strict quality control assessments.

CUSTOM DIET ADMINISTRATION

Taconic can administer custom-diets (medicated or

non-medicated) to any rodent model based on

your specifications.

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METABOLIC AND CARDIOVASCULAR DISEASE

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

TACONIC.COM

US: 1-888-822-6642EU: +45 70 23 04 05 [email protected]

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 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

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©Taconic Biosciences, Inc. All rights reserved. Contents of this publication may not be reproduced in any form without prior permission.