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Author Notes:

Correspondence: Kenneth E. Bernstein, M.D., Rm 7107A WMB, 101 Woodruff Circle, Emory University, Atlanta, GA 30322; Email: kbernst@emory.edu; Telephone: 404-727-3134; Fax: 404-712-9625

Subjects:

Research Funding:

The work was supported by NIH grants R37 DK039777, and R01 DK051445.

HDX is supported by a Scientist Development grant from the American Heart Association.

PL is supported by a Postdoctoral Fellowship from the American Heart Association.

SB is supported by grants from Fondation pour la Recherche Medicale (FRM) and Fondation Bettencourt.

SF is supported by a Beginning Grant-In-Aid from the American Heart Association and by F99 HL88000 from the NIH.

Keywords:

  • Angiotensin converting enzyme
  • Renin–angiotensin system
  • Mice
  • Macrophages
  • Heart

Tissue Specific Expression of Angiotensin Converting Enzyme: A new way to study an old friend

Tools:

Journal Title:

International Immunopharmacology

Volume:

Volume 8, Number 2

Publisher:

, Pages 171-176

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Angiotensin-converting enzyme (ACE) plays a central role in blood pressure regulation by producing the vasoconstrictor angiotensin II. When ACE knockout mice were studied, they presented with a complicated phenotype, including cardiovascular, reproductive, hematologic and developmental defects. The complexity of an ACE knockout mouse emphasizes the advantages and disadvantages of the classic knockout strategy. An animal lacking all ACE is very different from a wild type animal, and can be modeled as representing an extreme phenotype. To understand the role of ACE in a tissue and organ specific fashion, our group used targeted homologous recombination to create mouse models in which a promoter swapping strategy results in very restricted tissue patterns of ACE expression. Mice with ACE expression only in the heart, termed ACE 8/8 mice, present with atria enlargement and electrical conduction defects, but normal ventricular function. Mice with ACE expression only in monocytes and macrophages, termed ACE 10/10 mice, have a marked resistance to the growth of melanoma due to an enhanced immune response characterized by increased tumor specific CD8+ T cells and increased proinflammatory cytokines. These mice may define a new means of augmenting the immune response, potentially useful in human clinical situations. The promoter swapping strategy permits scientific investigation of questions unapproachable by other experimental approaches.

Copyright information:

© 2008 Elsevier

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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