top models for cardiovascular disease research webinar...

48
Top Mouse Models for Cardiovascular Disease Research Technical Information Services

Upload: others

Post on 26-Aug-2020

0 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

Top Mouse

Models for

Cardiovascular

Disease Research

Technical Information Services

Page 2: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

Upcoming JAX Webinars™

2

Designing and Optimizing Mouse Breeding Schemes

o February 4, 2016, 1 pm ET USA

Humanized Mice for Cancer Immunotherapy

o February 18, 2016, 9:00 am ET USA

o February 25, 2016, 1:00 pm ET USA

Achieving Reproducible Mouse Studies

o March 3, 2016, 1:00 pm ET USA

Comparing Immunodeficient Mice for Cancer, Immunity, and

Transplant Research

o March 10, 2016, 1:00 pm ET USA

www.jax.org/education-and-learning/webinars |

Subscribe to the monthly webinar announcements email list: https://subscribe.jax.org/

Page 4: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

The Jackson Laboratory’s Mission

4

Performing Research

Investigating genetics and biology of human disease

Providing Resources

JAX® Mice Clinical & Research Services, bioinformatics data,

technical publications and more…

Educating Scientists

World-class courses, internships and other programs

https://www.jax.org/education-and-learning |

Page 5: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

JAX® Mice The Gold Standard for Biomedical Research

JAX® Mice The Gold Standard for Biomedical Research

5

NIH funded resource

>8,000 strains and growing

o 2.7 million mice shipped annually

Unsurpassed genetic quality & animal health

Best characterized & referenced ~100 new pubs/week

Common inbred strains (C57BL/6J, BALB/cJ, DBA/2J) support

development/collection of specialty strains and other valuable

community research resources

JAX® Mice |

Page 6: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

Online Resources to Expedite

Research

6

JAX® Mice Database www.jax.org/jax-mice-and-services/

Mouse Genome Informatics www.informatics.jax.org

Mouse Phenome Database phenome.jax.org/

And many more unique

resources

Contact Technical Support |

Online Resources to Expedite

Research

Page 7: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

Cardiovascular Disease

7

Leading cause of morbidity

and mortality worldwide

(WHO)

Costs in the US

o $315 billion in 2010

o Projected to cost $2.8 trillion

by year 2030 (AHA 2014

update)

Coronary heart disease (Ischemic heart disease)

Cerebrovascular disease (stroke)

Peripheral arterial disease

Hypertension

Hypertrophy and Heart failure

Rheumatic heart disease

Congenital heart disease American

Heart

Association

Page 8: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

Mouse Models for Cardiovascular

Disease

Coronary heart disease

o Atherosclerosis

o Ischemic/reperfusion injury & myocardial

infarction

Hypertension

Hypertrophy and heart failure

Other heart abnormalities

JAX® Mice | 8

Page 9: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

JAX® Mice | 9

Sex Difference in Cardiovascular Disease Models

Sex differences in cardiovascular morbidity and mortality have long been

recognized. The mechanism is believed due largely to protective actions of

female hormones

Female mice are more tolerant to many cardiovascular injuries or stresses

than males

Do not mixed males and females in the same group

Mahmoodzadeh et al. 2012. Sex and Gender Differences in Pharmacology (214):23-48. [PMID: 23027444]

Page 10: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

Mouse Models for

Cardiovascular Disease

Coronary heart disease

o Atherosclerosis

o Ischemic/reperfusion injury & myocardial

infarction

Hypertension

Hypertrophy and heart failure

Other heart abnormalities

JAX® Mice | 10

Page 11: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

Atherosclerosis: Fatty artery wall deposits harden and block blood flow

Progressive disease

~ half a million people die

each year from the disease

Can lead to angina, heart

attack or stroke

Risk factors:

o High cholesterol, smoking, high

blood pressure, diabetes,

obesity and stress

http://www.nhlbi.nih.gov/health/dci/Diseases/Cad/CAD_WhatIs.html

JAX® Mice | 11

Page 12: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

Development of Atherosclerotic

Plaques

JAX® Mice |

Stage 1 Stage 2 Stage 3 Stage 4

Rader et al. 2008. Nature 451(7181):904-13. [PMID: 18288179]

12

Page 13: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

Lipoprotein Metabolism and

Transport

JAX® Mice |

Rader et al. 2008. Nature 451(7181):904-13. [PMID: 18288179]

13

Page 14: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

The Mouse as a Model for Human

Atherosclerosis

Advantages

Lipoprotein metabolism and transport pathways similar to humans

C57BL/6J susceptible to atherosclerotic lesions

Develop lesions on Atherogenic or Western diet

o BUT… lesions do not progress past fatty streak stage

o Can be genetically manipulated to develop atherosclerosis

Considerations

Lesions require several months to develop

Most plasma cholesterol stored in HDL, not LDL

JAX® Mice | 14

Page 15: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

Mouse Nomenclature

B6.129P2-Apoetm1Unc/J (002052)

Hypercholesterolemic (~ 400 mg/dl)

Increased circulating VLDL and LDL cholesterol

Decreased circulating HDL cholesterol

Spontaneously develop arterial lesions

o 3 months: fatty streaks in proximal aorta

o 13 months: atherosclerotic lesions

Ishida T et al. 2004. J Biol Chem 279(43):45085-92 [PMID: 15304490]

Moghadasian M et al. 2001. FASEB J 15(14):2623-30 [PMID: 11726538]

Ma Z et al. 2008. Clin Immunol 127(2):168-75 [PMID: 18325838]

JAX® Mice |

Spontaneous Atherosclerosis in ApoE

Null Mice (Normal “Chow” Diet)

15

Page 16: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

Other JAX atherosclerosis susceptible mice

JAX® Mice

B6.129P2-Apoetm1Unc/J (002052)

Aortic plaques at 8 months of age

Elevated total & HDL cholesterol

Elevated Triglycerides

ApoE -/- ApoE +/-

Genotype Total

Chol

HDL

Chol

Triglyc

Wild-type 88 78 73

ApoE -/- 750 270 282

16

Spontaneous Atherosclerosis in ApoE

Null Mice (Normal “Chow” Diet)

Page 17: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

Diets-Induced Atherosclerosis

Atherogenic (Paigen) Diet*

15% butter fat

1-1.25% cholesterol

0.5% cholic acid

50% sucrose

20% casein

JAX® Mice |

Western Diet

21% butter fat

0.2% cholesterol

0% cholic acid

34% sucrose

19.5% casein

*Cholesterol 10-20 times normal, cholic acid is pro-inflammatory

17

JAX mice susceptible to diets-induced atherosclerosis

JAX mice relatively resistant to diets-induced atherosclerosis

Page 18: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

Diet Induced Athersclerosis in B6J Atherosclerotic (Paigen) Diet

Cholesterol 200-300 mg/dl (B6 females on chow = 80-90 mg/ml)

Lesions form by 7 weeks, thickened arterial wall and cell proliferation

By 14 weeks, fatty streaks with lipid filled cells and cuboidal nuclei

Lesions form in ascending aorta/aortic sinus

Mice survive to 28-40 weeks on diet

Paigen et al. 1990. Arteriosclerosis 10(2):316-23. [PMID: 2317166]

Normal 7 weeks 14 weeks

18

Page 19: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

Diet Induced Athersclerosis in B6J Monocytes Exacerbates & IL-10 Alleviates Lesion

Development

Walker et al. 1999. Arterioscler Thromb Biol. 19(11):2673-9. [PMID: 10559010]

Mallat et al. 1999. Circ Res. 85(8):17-24. [PMID: 10521249]

16 weeks (Sirius Red/Collagen) 9 weeks (CD11b+ monocytes/red)

treated untreated IL-10 -/- IL-10 +/+

3-Deazaadenosine Treatment

Inhibition of monocyte chemotaxis & adhesion

Decreased number and size of lesions in

treated mice (fewer monocytes in lesions)

Normal B6 vs B6 IL-10 -/- (002251)

IL-10 is protective for lesion development

Increased number and size of lesions in the

IL-10 -/- mice

19

Page 20: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

Atherogenic Diet (14 weeks)

Normal Diet (14 weeks)

Plaques on the aortic luminal

surface of 24 week old mice

B6.129P2-Apoetm1Unc/J (002052)

(15.8% fat, 1.25% cholesterol, 0.5% Na cholate)

Abundant, large plaques by 14 weeks

Increased plasma VLDL cholesterol

Increased plasma total cholesterol

Guo Y et al. 2005. Hear Res 208(1-2):54-67 [PMID: 16051453]

Ishida T et al. 2004. J Biol Chem 279(43):45085-92 [PMID: 15304490]

Ma Z et al. 2008. Clin Immunol 127(2):168-75 [PMID: 18325838]

JAX® Mice |

Atherosclerosis in ApoE Null Mice Accelerated Disease on an Atherogenic “Paigen” Diet

20

Page 21: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

Apoe +/+

Apoe -/-

(athero diet)

Apoe -/-

Rati

o o

f in

tim

a t

o m

ed

ia (

I/M

)

Apoe +/+ Apoe -/- Apoe -/-

(athero diet) aortic sinus ascending aorta

Guo Y et al. 2005. Hear Res 208(1-2):54-67 [PMID: 16051453]

http://www.web-books.com/eLibrary/Medicine/Physiology/Cardiovascular/artery.jpg

JAX® Mice |

Atherosclerosis in ApoE Null Mice Accelerated Disease on an Atherogenic “Paigen” Diet

21

Page 22: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

Ishibashi et al. 1994. J Clin Invest. 93(5):1885-93. [PMID: 8182121]

JAX® Mice |

Atherosclerosis in Ldlr Null Mice Atherogenic “Paigen” Diet Required for Atherosclerosis

Comparison of Normal Chow to Atherogenic Diet

B6.129S7-Ldlrtm1Her/J (002207)

Elevated total cholesterol on normal chow, no atherosclerosis

Hypercholesterolemia on atherogenic diet, increased VLDL and decreased HDL

22

Cholesterol

Page 23: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

Ishibashi et al. 1994. J Clin Invest. 93(5):1885-93. [PMID: 8182121]

JAX® Mice |

Atherosclerosis in Ldlr Null Mice Atherogenic “Paigen” Diet Required for Atherosclerosis

B6.129S7-Ldlrtm1Her/J (002207)

No gross lesions in aorta of wild-type or

Ldlr -/- fed normal chow

Only Ldlr -/- fed atherogenic high

cholesterol diet showed plaques

Ldlr -/- fed atherogenic diet had severe

xanthomas

13 months of age, 8 months on diet

23

Page 24: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

New Atherosclerosis Model “E4H”

Mouse Apoe replaced with human apoE4 isoform

Mouse Ldlr replaced with human LDLR

Highly sensitive to diet-induced dyslipidemia

Hypercholesterolemia

Atherosclerosis

Malloy SI et al. 2004. Arterioscler Thromb Vasc Biol 24 (1) 91-7 [PubMed: 12969990]

24

B6.129-Apoetm3(APOE*4)Mae Ldlrtm1(LDLR)Mae/J (012307)

On a high fat diet:

Page 25: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

Mouse Models for

Cardiovascular Disease

Coronary heart disease

o Atherosclerosis

o Ischemic/reperfusion injury & myocardial

infarction

Hypertension

Hypertrophy and heart failure

Other heart abnormalities

JAX® Mice | 25

Page 26: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

JAX® Mice | 26

Ischemia/Reperfusion (I/R) Injury and

Myocardial Infarction (MI)

Image created by J. Heuser, 2006

Acute MI is also known as a “heart attack”

Infarction: tissue death

Ischemia: lack of blood and oxygen supply

Reperfusion: restore of blood supply

Infarction area of the tip of the

anterior wall of the heart

Atherosclerosis

Thrombosis

Coronary

artery spasm

Coronary

occlusion

Page 27: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

JAX® Mice | 27

In Vivo Experimental Models for I/R

or MI

Complied from Terese Winslow, Lydia Kibiuk 2001

Ligation of the left anterior descending (LAD)

coronary artery

Coronary artery occlusion

Readouts

Infarct size

Functional (or contractility)

recovery

Biomarkers for tissue damage Troponin I/T, CK and LDH activity, etc.

Page 28: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

JAX® Mice | 28

I/R or MI Models Genetic Background Difference

FVB/NJ and ICR are resistant to I/R injury (increase occlusion time)

C57BL/6J and B6/129Sv/D2 are susceptible to I/R injury (decrease occlusion time)

Guo et al. 2012 Basic Res Cardiol. [PMID: 22864681]

Page 29: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

Mouse Models for

Cardiovascular Disease

Coronary heart disease

o Atherosclerosis

o Ischemic/reperfusion & myocardial

infarction

Hypertension

Hypertrophy and heart failure

Other heart abnormalities

JAX® Mice | 29

Page 30: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

Hypertension

Definition:

o systolic BP of 140 mmHg or greater

o diastolic BP of 90 mmHg or greater

> 50 million Americans suffer from hypertension

Increases risk of coronary heart disease, congestive heart failure, stroke and kidney disease

Contributing factors:

o Obesity

o Salt sensitivity

o Insulin resistance

o Genetic factors

o Age

JAX® Mice | 30

Page 31: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

Inbred Strains for BP Research

Mouse Nomenclature

BPH/2J (003005) Hypertensive

BPL/1J (003006) Hypotensive

BPN/3J (003004) Normotensive

BPH vs. BPL & BPN

Elevated systolic BP by 5 weeks

~ 60 mmHg higher by 5 months

Elevated heart rates, enlarged hearts and kidneys, and higher

hematocrit

3-5 genes contributing to BP differences

Data in Mouse Phenome Database (MPD)

Schlager G and Sides J. 1997. Lab Animal Sci 47(3):288-92. [PMID: 9241632]

Uddin M et al. 2003. Mech Ageing Dev 124(7):811-7 [PMID: 12875744]

JAX® Mice | 31

Page 32: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

B6 Agtr1a Null

Mouse Nomenclature

B6.129P2-Agtr1atm1Unc/J (002682)

Angiotensin 2 receptor 1a

Regulates sodium and fluid

homeostasis

Arterial pressure reduced by

~43 mmHg

Systolic BP reduced by ~24

mmHg

BP sensitive to [Na+]

Ito M et al. 1995. PNAS 92(8):3521-5 [PMID: 7724593]

JAX® Mice | 32

Page 33: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

Mouse Models for

Cardiovascular Disease

Coronary heart disease

o Atherosclerosis

o Ischemic/reperfusion & myocardial

infarction

Hypertension

Hypertrophy and heart failure

Other heart abnormalities

JAX® Mice | 33

Page 34: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

Hypertrophy and Heart Failure

JAX® Mice | 34

Hypertrophic cardiomyopathy

o The second most common form of heart muscle disease

o Genetically transmitted or induced

Heart failure

o Heart muscle weakened and cannot pump enough blood to the rest of the body

o Caused by conditions that damaged the heart muscle or overwork the heart

00

Decompensation

00 Figure compiled from Abcam.com

Atherosclerosis

Hypertension

Myocardial infarction

Other injuries or stress

Heart overworked

weakened and

enlarged

Page 35: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

Hypertrophy and Heart Failure Common Experimental Models

JAX® Mice | 35

Jianyong et al. 2014 Evid Based Complement Alternat Med. [PMID: 25093027]

deAlmeida et al. 2010 J Vis Exp (38): 1729. [PMID: 3164086]

Weinheimer et al. 2015. Clin Exp Pharmacol Physiol 42(1):33-40 [PMID: 25311547]

Crowley et al. 2006 PNAS 103(47):17985-90. [PMID: 17090678]

Transverse Aortic Constriction (TAC):

Permanent MI (or combination of TAC and MI)

Angiotensin II infusion Readouts

Heart weight

Heart function

Heart wall thickness

Chamber size

Fibrosis

TAC Sham TAC position

Page 36: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

B6 substrains Different Responses to TAC-induced Hypertrophy

JAX® Mice | 36

B6 substrains compared

o C57BL/6J (JL)

o C57BL/6NCrl (CL)

o C57BL/6NTac (TF)

Garcia-Menendez et al., 2013 Am J Physiol Heart Circ Physiol. 305(3): H397–H402. [PMID: 23709599]

Page 37: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

JAX® Mice | 37

C57BL/6J is more tolerant to TAC-

induced hypertrophy

o Better survival

o Better heart function

o Less increase in heart weight

o Less wall thickness and dilation

Garcia-Menendez et al., 2013 Am J Physiol Heart Circ Physiol. 305(3): H397–H402. [PMID: 23709599]

B6 substrains Different Responses to TAC-induced Hypertrophy

C57BL/6J may more useful in studies

o Longer time

o Factors that make accelerate and

acerbate hypertrophy

Page 38: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

B6 Nos3 Null (eNOS)

Mouse Nomenclature

B6.129P2-Nos3tm1Unc/J (002684)

C57BL/6J background

~140 mm Hg (~20 mmHg higher BP than

controls) by 12–16 weeks or age

After TAC*, mutant hearts show only

modest and concentric cardiac hypertrophy

by 3 weeks

Impaired pulmonary angiogenesis

Increased left ventricle systolic pressure

Shesely EG et al. 1996. PNAS 93(23):13176-81 [PMID: 8917564]

Takimoto E et al. 2005. J Clin Invest 115(5):1221-31 [PMID: 15841206]

Han RN et al. 2004. Circ Res 94(8):1115-23 [PMID: 15016731]

JAX® Mice |

*Transverse Aortic Constriction

38

Page 39: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

JAX® Mice | 39

D’Angelo et al., 1997 PNAS. 94(15):8121-6. [PMID: 9223325]

Cardiac-specific Gαq Transgenic

mice

Mouse Nomenclature

FVB/N-Tg(Myh6-Gnaq)40Gwd/J

(012460)

Gαq is regulated by an α-myosin

heavy chain (Myh6) promoter

Enlarged heart

Increased cardiomyocytes size

Severely compromised systolic

function

Overt heart failure Transgenic Non-transgenic sibling

Page 40: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

Mouse Models for

Cardiovascular Disease

Coronary heart disease

o Atherosclerosis

o Ischemic/reperfusion & myocardial

infarction

Hypertension

Hypertrophy and heart failure

Other heart abnormalities

JAX® Mice | 40

Page 41: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

JAX® Mice | 41

Other Cardiomyopathies

Arrhythmia

o Bradycardia

o Tachycardia

Aortic aneurysm

o B6.129-Fbn1tm1Hcd/J (012885)

o B6.129S4-Timp1tm1Pds/J (006243)

Metabolic Syndrome

o B6.Cg-Lepob Ldlrtm1Her/J (006906)

o BKS.Cg-Leprdb Nos3tm1Unc/RhrsJ (008340)

Vascular Defects

Page 42: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

JAX® Mice | 42

Cardiovascular Tool Strains

Cre Recombinase Expressing:

o Smooth muscle

B6.129S6-Taglntm2(cre)Yec/J (006878)

o Inducible in cardiomyocytes

B6.FVB(129)-Tg(Myh6-cre/Esr1*)1Jmk/J (005657)

o Endothelium of developing and quiescent vessels

B6.FVB-Tg(Cdh5-cre)7Mlia/J (006137)

o Cardiac muscle cells

B6.FVB-Tg(Myh6-cre)2182Mds/J (011038)

Fluorescent Protein Expressing:

o mCherry expression in cardiomyocytes

B6;D2-Tg(Myh6*-mCherry)2Mik/J (021577)

o GFP in endothelial cells

STOCK Tg(TIE2GFP)287Sato/J (003658)

Page 48: Top Models for Cardiovascular Disease Research webinar ...jackson.jax.org/rs/444-BUH-304/images/... · o February 4, 2016, 1 pm ET USA Humanized Mice for Cancer Immunotherapy o February

Thank you!

48

In need of mouse breeding and colony

management expertise to advance your

research?

Contact your regional representative today

www.jax.org/jaxmice/support/regionalcontacts

Contact technical support

www.jax.org/jax-mice-and-services/customer-support/technical-support

JAX® Mice, Clinical & Research Services

1-800-422-6423 • 1-207-288-5845

[email protected] • www.jax.org/jax-mice-and-services