Cardiomyocyte-Specific Endothelin A Receptor Knockout Mice Have Normal Cardiac Function and an Unaltered Hypertrophic Response to Angiotensin II and Isoproterenol

Rafal Kedzierski, Paul A. Grayburn, Yaz Y. Kisanuki, Clay S. Williams, Robert E. Hammer, James A. Richardson, Micheal D. Schneider, Masashi Yanagisawa

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Even though endothelin is recognized as an important vasoregulatory molecule, the roles of endothelin receptors in specific cell types are not yet fully understood. Mice with a null mutation in endothelin A receptor gene (ETA) or in the gene of its ligand (endothelin 1) die neonatally due to craniofacial and cardiac abnormalities. This early lethality has in the past hindered studies on the role of endothelin in cardiovascular physiology and pathophysiology. To overcome this obstacle, we utilized the cre/loxP technology to generate mice in which the ETA gene could be deleted specifically in cardiomyocytes. The cre recombinase transgene driven by the α-myosin heavy-chain promoter deleted the floxed ETA allele specifically in the hearts of these mice, resulting in a 78% reduction in cardiac ET A mRNA level compared to wild-type controls. Cardiomyocyte-specific ETA knockout animals are viable and exhibit normal growth, cardiac anatomy, and cardiac contractility, as assessed by echocardiography. In addition, these animals exhibit hypertrophic and contractile responses to 10-day infusion of angiotensin II or isoproterenol similar to those observed in control animals. These results indicate that in adult mice cardiac ET A receptors are not necessary for either baseline cardiac function or stress-induced response to angiotensin II or isoproterenol.

Original languageEnglish (US)
Pages (from-to)8226-8232
Number of pages7
JournalMolecular and cellular biology
Volume23
Issue number22
DOIs
StatePublished - Nov 1 2003

Fingerprint

Endothelin A Receptors
Isoproterenol
Cardiac Myocytes
Knockout Mice
Angiotensin II
Endothelins
Craniofacial Abnormalities
Cardiovascular Physiological Phenomena
Genes
Endothelin Receptors
Myosin Heavy Chains
Endothelin-1
Transgenes
Echocardiography
Anatomy
Alleles
Ligands
Technology
Messenger RNA
Mutation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Cardiomyocyte-Specific Endothelin A Receptor Knockout Mice Have Normal Cardiac Function and an Unaltered Hypertrophic Response to Angiotensin II and Isoproterenol. / Kedzierski, Rafal; Grayburn, Paul A.; Kisanuki, Yaz Y.; Williams, Clay S.; Hammer, Robert E.; Richardson, James A.; Schneider, Micheal D.; Yanagisawa, Masashi.

In: Molecular and cellular biology, Vol. 23, No. 22, 01.11.2003, p. 8226-8232.

Research output: Contribution to journalArticle

Kedzierski, Rafal ; Grayburn, Paul A. ; Kisanuki, Yaz Y. ; Williams, Clay S. ; Hammer, Robert E. ; Richardson, James A. ; Schneider, Micheal D. ; Yanagisawa, Masashi. / Cardiomyocyte-Specific Endothelin A Receptor Knockout Mice Have Normal Cardiac Function and an Unaltered Hypertrophic Response to Angiotensin II and Isoproterenol. In: Molecular and cellular biology. 2003 ; Vol. 23, No. 22. pp. 8226-8232.
@article{402a0f96df2a48d48e40c9096de27dbe,
title = "Cardiomyocyte-Specific Endothelin A Receptor Knockout Mice Have Normal Cardiac Function and an Unaltered Hypertrophic Response to Angiotensin II and Isoproterenol",
abstract = "Even though endothelin is recognized as an important vasoregulatory molecule, the roles of endothelin receptors in specific cell types are not yet fully understood. Mice with a null mutation in endothelin A receptor gene (ETA) or in the gene of its ligand (endothelin 1) die neonatally due to craniofacial and cardiac abnormalities. This early lethality has in the past hindered studies on the role of endothelin in cardiovascular physiology and pathophysiology. To overcome this obstacle, we utilized the cre/loxP technology to generate mice in which the ETA gene could be deleted specifically in cardiomyocytes. The cre recombinase transgene driven by the α-myosin heavy-chain promoter deleted the floxed ETA allele specifically in the hearts of these mice, resulting in a 78{\%} reduction in cardiac ET A mRNA level compared to wild-type controls. Cardiomyocyte-specific ETA knockout animals are viable and exhibit normal growth, cardiac anatomy, and cardiac contractility, as assessed by echocardiography. In addition, these animals exhibit hypertrophic and contractile responses to 10-day infusion of angiotensin II or isoproterenol similar to those observed in control animals. These results indicate that in adult mice cardiac ET A receptors are not necessary for either baseline cardiac function or stress-induced response to angiotensin II or isoproterenol.",
author = "Rafal Kedzierski and Grayburn, {Paul A.} and Kisanuki, {Yaz Y.} and Williams, {Clay S.} and Hammer, {Robert E.} and Richardson, {James A.} and Schneider, {Micheal D.} and Masashi Yanagisawa",
year = "2003",
month = "11",
day = "1",
doi = "10.1128/MCB.23.22.8226-8232.2003",
language = "English (US)",
volume = "23",
pages = "8226--8232",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "22",

}

TY - JOUR

T1 - Cardiomyocyte-Specific Endothelin A Receptor Knockout Mice Have Normal Cardiac Function and an Unaltered Hypertrophic Response to Angiotensin II and Isoproterenol

AU - Kedzierski, Rafal

AU - Grayburn, Paul A.

AU - Kisanuki, Yaz Y.

AU - Williams, Clay S.

AU - Hammer, Robert E.

AU - Richardson, James A.

AU - Schneider, Micheal D.

AU - Yanagisawa, Masashi

PY - 2003/11/1

Y1 - 2003/11/1

N2 - Even though endothelin is recognized as an important vasoregulatory molecule, the roles of endothelin receptors in specific cell types are not yet fully understood. Mice with a null mutation in endothelin A receptor gene (ETA) or in the gene of its ligand (endothelin 1) die neonatally due to craniofacial and cardiac abnormalities. This early lethality has in the past hindered studies on the role of endothelin in cardiovascular physiology and pathophysiology. To overcome this obstacle, we utilized the cre/loxP technology to generate mice in which the ETA gene could be deleted specifically in cardiomyocytes. The cre recombinase transgene driven by the α-myosin heavy-chain promoter deleted the floxed ETA allele specifically in the hearts of these mice, resulting in a 78% reduction in cardiac ET A mRNA level compared to wild-type controls. Cardiomyocyte-specific ETA knockout animals are viable and exhibit normal growth, cardiac anatomy, and cardiac contractility, as assessed by echocardiography. In addition, these animals exhibit hypertrophic and contractile responses to 10-day infusion of angiotensin II or isoproterenol similar to those observed in control animals. These results indicate that in adult mice cardiac ET A receptors are not necessary for either baseline cardiac function or stress-induced response to angiotensin II or isoproterenol.

AB - Even though endothelin is recognized as an important vasoregulatory molecule, the roles of endothelin receptors in specific cell types are not yet fully understood. Mice with a null mutation in endothelin A receptor gene (ETA) or in the gene of its ligand (endothelin 1) die neonatally due to craniofacial and cardiac abnormalities. This early lethality has in the past hindered studies on the role of endothelin in cardiovascular physiology and pathophysiology. To overcome this obstacle, we utilized the cre/loxP technology to generate mice in which the ETA gene could be deleted specifically in cardiomyocytes. The cre recombinase transgene driven by the α-myosin heavy-chain promoter deleted the floxed ETA allele specifically in the hearts of these mice, resulting in a 78% reduction in cardiac ET A mRNA level compared to wild-type controls. Cardiomyocyte-specific ETA knockout animals are viable and exhibit normal growth, cardiac anatomy, and cardiac contractility, as assessed by echocardiography. In addition, these animals exhibit hypertrophic and contractile responses to 10-day infusion of angiotensin II or isoproterenol similar to those observed in control animals. These results indicate that in adult mice cardiac ET A receptors are not necessary for either baseline cardiac function or stress-induced response to angiotensin II or isoproterenol.

UR - http://www.scopus.com/inward/record.url?scp=0242664032&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0242664032&partnerID=8YFLogxK

U2 - 10.1128/MCB.23.22.8226-8232.2003

DO - 10.1128/MCB.23.22.8226-8232.2003

M3 - Article

VL - 23

SP - 8226

EP - 8232

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 22

ER -