Mouse Models for Cardiovascular Research

Our strong track record illustrates our extensive experience and dedication to develop rodent models as genetic tools for the study of medical cardiovascular conditions such as myocardial infarction, arteriosclerosis, arrhythmia, angiogenesis, hypertension, thrombosis, to mention a few.

We have been providing "cardiovascular" models to scientists from academic institutions (Charité University Berlin, Imperial College London, Emory University, Frankfurt University, Harvard Medical School, Heidelberg University, King's College London, Max Planck Institute, The Welcome Trust Center Oxford, etc.), pharmaceutical industries and biotechnology companies (AstraZeneca, Bayer HealthCare, BMS, Boehringer Ingelheim, Merck KGaA, Sanofi-Aventis, etc.) for studying:

  • Cardiovascular functions under both normal and pathologic conditions.
  • Drug targets (humanization of receptor and signaling molecules, monitoring of pathway activations, etc.).

Do not hesitate to contact our scientific experts to discuss any project you have in mind. You will, at no expense to you, be able to evaluate what our experience, expertise and technologies for the design of genetically modified models will bring of value to your project.


Below you will find a selection of references for models we have created for our clients:

Cardiovascular Conditions

Von Willebrand disease type 2b:
Adam F, Casari C, Prévost N, Kauskot A, Loubière C, Legendre P, Repérant C, Baruch D, Rosa JP, Bryckaert M, de Groot PG, Christophe OD, Lenting PJ, Denis CV.
A genetically-engineered von Willebrand disease type 2B mouse model displays defects in hemostasis and inflammation.
Sci Rep. 2016

Cardio protection:
Parra S, Huang X, Charbeneau RA, Wade SM, Kaur K, Rorabaugh BR, Neubig RR
Conditional disruption of interactions between Gαi2 and regulator of G protein signaling (RGS) proteins protects the heart from ischemic injury.
BMC Pharmacol Toxicol. 2014

Hinkel R, Penzkofer D, Zühlke S, Fischer A, Husada W, Xu QF, Baloch E, van Rooij E, Zeiher AM, Kupatt C, Dimmeler S.
Inhibition of MicroRNA-92a Protects Against Ischemia-Reperfusion Injury in a Large Animal Model.
Circulation. 2013

Arteriosclerotic disease:
Goettsch C, Hutcheson JD, Hagita S, Rogers MA, Creager MD, Pham T, Choi J, Mlynarchik AK, Pieper B, Kjolby M, Aikawa M, Aikawa E.
A single injection of gain-of-function mutant PCSK9 adeno-associated virus vector induces cardiovascular calcification in mice with no genetic modification.
Atherosclerosis. 2016

Margariti A, Li H, Chen T, Martin D, Vizcay-Barrena G, Alam S, Karamariti E, Xiao Q, Zampetaki A, Zhang Z, Wang W, Jiang Z, Gao C, Ma B, Chen YG, Cockerill G, Hu Y, Xu Q, Zeng L.
XBP1 mRNA Splicing Triggers an Autophagic Response in Endothelial Cells through BECLIN-1 Transcriptional Activation.
J Biol Chem. 2013

Congenital heart disease:
Thomas PS, Rajderkar S, Lane J, Mishina Y, Kaartinen V
AcvR1-mediated BMP signaling in second heart field is required for arterial pole development: Implications for myocardial differentiation and regional identity.
Dev Biol. 2014 Jun 15.

Helmer RA, Martínez-Zaguilán R, Dertien JS, Fulford C, Foreman O, Peiris V, Chilton BS.
Helicase-like transcription factor (hltf) regulates g2/m transition, wt1/gata4/hif-1a cardiac transcription networks, and collagen biogenesis.
PLoS One. 2013

Chen CM, Bentham J, Cosgrove C, Braganca J, Cuenda A, Bamforth SD, Schneider JE, Watkins H, Keavney B, Davies B, Bhattacharya S.
Functional Significance of SRJ Domain Mutations in CITED2.
PLoS One. 2012

Arrhythmia:
Pavlovic D, Hall AR, Kennington EJ, Aughton K, Boguslavskyii A, Fuller W, Despa S, Bers DM, Shattock MJ.
Nitric oxide regulates cardiac intracellular Na+ and Ca2+ by modulating Na/K ATPase via PKCε and phospholemman-dependent mechanism.
J Mol Cell Cardiol. 2013

Angiogenesis:
Dowsett L, Piper S, Slaviero A, Dufton N, Wang Z, Boruc O, Delahaye M, Colman L, Kalk E, Tomlinson J, Birdsey G, Randi AM, Leiper J.
Endothelial Dimethylarginine Dimethylaminohydrolase 1 Is an Important Regulator of Angiogenesis but Does Not Regulate Vascular Reactivity or Hemodynamic Homeostasis.
Circulation. 2015

Fantin A, Herzog B, Mahmoud M, Yamaji M, Plein A, Denti L, Ruhrberg C, Zachary I.
Neuropilin 1 (NRP1) hypomorphism combined with defective VEGF-A binding reveals novel roles for NRP1 in developmental and pathological angiogenesis.
Development. 2014

Zeng L, Xiao Q, Chen M, Margariti A, Martin D, Ivetic A, Xu H, Mason J, Wang W, Cockerill G, Mori K, Li JY, Chien S, Hu Y, Xu Q.
Vascular endothelial cell growth-activated XBP1 splicing in endothelial cells is crucial for angiogenesis.
Circulation. 2013

Kovacevic I, Hu J, Siehoff-Icking A, Opitz N, Griffin A, Perkins AC, Munn AL, Müller-Esterl W, Popp R, Fleming I, Jungblut B, Hoffmeister M, Oess S.
The F-BAR protein NOSTRIN participates in FGF signal transduction and vascular development.
EMBO J. 2012

Hypertension:
Patrick Davis R, Linder AE, Watts SW.
Lack of the serotonin transporter (SERT) reduces the ability of 5-hydroxytryptamine to lower blood pressure.
Naunyn Schmiedebergs Arch Pharmacol. 2011

Vascular homeostasis:
Moyes AJ, Khambata RS, Villar I, Bubb KJ, Baliga RS, Lumsden NG, Xiao F, Gane PJ, Rebstock AS, Worthington RJ, Simone MI, Mota F, Rivilla F, Vallejo S, Peiró C, Sánchez Ferrer CF, Djordjevic S, Caulfield MJ, MacAllister RJ, Selwood DL, Ahluwalia A, Hobbs AJ
Endothelial C-type natriuretic peptide maintains vascular homeostasis.
J Clin Invest. 2014

Vascular permeability:
Frye M, Dierkes M, Küppers V, Vockel M, Tomm J, Zeuschner D, Rossaint J, Zarbock A, Koh GY, Peters K, Nottebaum AF, Vestweber D.
Interfering with VE-PTP stabilizes endothelial junctions in vivo via Tie-2 in the absence of VE-cadherin.
J Exp Med. 2015

Coronary arterial calcification:
Goettsch C, Hutcheson JD, Aikawa M, Iwata H, Pham T, Nykjaer A, Kjolby M, Rogers M, Michel T, Shibasaki M, Hagita S, Kramann R, Rader DJ, Libby P, Singh SA, Aikawa E.
Sortilin mediates vascular calcification via its recruitment into extracellular vesicles.
J Clin Invest. 2016

Medial vascular calcification:
Sheen CR, Kuss P, Narisawa S, Yadav MC, Nigro J, Wang W, Chhea TN, Sergienko EA, Kapoor K, Jackson MR, Hoylaerts MF, Pinkerton AB, O'Neill WC, Millán JL.
Pathophysiological role of vascular smooth muscle alkaline phosphatase in medial artery calcification.
J Bone Miner Res. 2015

Laminar shear stress:
Sánchez-Gómez FJ, Calvo E, Bretón-Romero R, Fierro-Fernández M, Anilkumar N, Shah AM, Schröder K, Brandes RP, Vázquez J, Lamas S.
NOX4-dependent Hydrogen peroxide promotes shear stress-induced SHP2 sulfenylation and eNOS activation.
Free Radic Biol Med. 2015.

Cardiac failure:
Zhang M, Brewer AC, Schröder K, Santos CX, Grieve DJ, Wang M, Anilkumar N, Yu B, Dong X, Walker SJ, Brandes RP, Shah AM.
NADPH oxidase-4 mediates protection against chronic load-induced stress in mouse hearts by enhancing angiogenesis.
Proc Natl Acad Sci U S A. 2010

Smart N, Risebro CA, Melville AA, Moses K, Schwartz RJ, Chien KR, Riley PR.
Thymosin beta4 induces adult epicardial progenitor mobilization and neovascularization.
Nature. 2007

Thrombosis:
Zhou J, Wu Y, Wang L, Rauova L, Hayes VM, Poncz M, Essex DW.
The C-terminal CGHC motif of protein disulfide isomerase supports thrombosis.
J Clin Invest. 2015

Kim K, Hahm E, Li J, Holbrook LM, Sasikumar P, Stanley RG, Ushio-Fukai M, Gibbins JM, Cho J.
Platelet protein disulfide isomerase is required for thrombus formation but not for hemostasis in mice.
Blood. 2013

Hemophilia A, F8 deficiency:
Fahs SA, Hille MT, Shi Q, Weiler H, Montgomery RR
A conditional knockout mouse model reveals endothelial cells as the principal and possibly exclusive source of plasma factor VIII.
Blood. 2014

Cardiac malformation:
MacDonald ST, Bamforth SD, Chen CM, Farthing CR, Franklyn A, Broadbent C, Schneider JE, Saga Y, Lewandoski M, Bhattacharya S.
Epiblastic Cited2 deficiency results in cardiac phenotypic heterogeneity and provides a mechanism for haploinsufficiency
Cardiovasc Res. 2008

Model Creation Services

Conditional Knockout (Learn more):
Frye M, Dierkes M, Küppers V, Vockel M, Tomm J, Zeuschner D, Rossaint J, Zarbock A, Koh GY, Peters K, Nottebaum AF, Vestweber D.
Interfering with VE-PTP stabilizes endothelial junctions in vivo via Tie-2 in the absence of VE-cadherin.
J Exp Med. 2015

Dowsett L, Piper S, Slaviero A, Dufton N, Wang Z, Boruc O, Delahaye M, Colman L, Kalk E, Tomlinson J, Birdsey G, Randi AM, Leiper J.
Endothelial Dimethylarginine Dimethylaminohydrolase 1 Is an Important Regulator of Angiogenesis but Does Not Regulate Vascular Reactivity or Hemodynamic Homeostasis.
Circulation. 2015

Zhou J, Wu Y, Wang L, Rauova L, Hayes VM, Poncz M, Essex DW.
The C-terminal CGHC motif of protein disulfide isomerase supports thrombosis.
J Clin Invest. 2015

Fahs SA, Hille MT, Shi Q, Weiler H, Montgomery RR
A conditional knockout mouse model reveals endothelial cells as the principal and possibly exclusive source of plasma factor VIII.
Blood. 2014

Hinkel R, Penzkofer D, Zühlke S, Fischer A, Husada W, Xu QF, Baloch E, van Rooij E, Zeiher AM, Kupatt C, Dimmeler S.
Inhibition of MicroRNA-92a Protects Against Ischemia-Reperfusion Injury in a Large Animal Model.
Circulation. 2013

Safe Knockout (Learn more):
Zeng L, Xiao Q, Chen M, Margariti A, Martin D, Ivetic A, Xu H, Mason J, Wang W, Cockerill G, Mori K, Li JY, Chien S, Hu Y, Xu Q.
Vascular endothelial cell growth-activated XBP1 splicing in endothelial cells is crucial for angiogenesis.
Circulation. 2013

Kovacevic I, Hu J, Siehoff-Icking A, Opitz N, Griffin A, Perkins AC, Munn AL, Müller-Esterl W, Popp R, Fleming I, Jungblut B, Hoffmeister M, Oess S.
The F-BAR protein NOSTRIN participates in FGF signal transduction and vascular development.
EMBO J. 2012

Reporter/Tag Knockin (Learn more):
Koechlein CS, Harris JR, Lee TK, Weeks J, Fox RG, Zimdahl B, Ito T, Blevins A, Jung SH, Chute JP, Chourasia A, Covert MW, Reya T.
High-resolution imaging and computational analysis of haematopoietic cell dynamics in vivo.
Nat Commun. 2016

Point Mutation Knockin (Learn more):
Adam F, Casari C, Prévost N, Kauskot A, Loubière C, Legendre P, Repérant C, Baruch D, Rosa JP, Bryckaert M, de Groot PG, Christophe OD, Lenting PJ, Denis CV.
A genetically-engineered von Willebrand disease type 2B mouse model displays defects in hemostasis and inflammation.
Sci Rep. 2016

Permissive Locus HPRT Knockin (Learn more):
Sheen CR, Kuss P, Narisawa S, Yadav MC, Nigro J, Wang W, Chhea TN, Sergienko EA, Kapoor K, Jackson MR, Hoylaerts MF, Pinkerton AB, O'Neill WC, Millán JL.
Pathophysiological role of vascular smooth muscle alkaline phosphatase in medial artery calcification.
J Bone Miner Res. 2015

Smart N, Risebro CA, Melville AA, Moses K, Schwartz RJ, Chien KR, Riley PR.
Thymosin beta4 induces adult epicardial progenitor mobilization and neovascularization.
Nature. 2007

Rat Pronuclear Injection:
Pavlovic D, Hall AR, Kennington EJ, Aughton K, Boguslavskyii A, Fuller W, Despa S, Bers DM, Shattock MJ.
Nitric oxide regulates cardiac intracellular Na+ and Ca2+ by modulating Na/K ATPase via PKCε and phospholemman-dependent mechanism.
J Mol Cell Cardiol. 2013