Replacement by Homologous Recombination of the <i>minK</i> Gene With <i>lacZ</i> Reveals Restriction of <i>minK</i> Expression to the Mouse Cardiac Conduction System

DOI Web Site 被引用文献2件
  • Sabina Kupershmidt
    From the Departments of Medicine (S.K., T.Y., M.E.A., M.A.M., D.M.R.), Pharmacology (S.K., T.Y., M.E.A., D.M.R.), and Molecular Physiology & Biophysics (K.D.N., M.A.M.), Vanderbilt University School of Medicine, Nashville, Tenn, and Department of Cell Biology and Anatomy (A.W.), Medical University of South Carolina, SC.
  • Tao Yang
    From the Departments of Medicine (S.K., T.Y., M.E.A., M.A.M., D.M.R.), Pharmacology (S.K., T.Y., M.E.A., D.M.R.), and Molecular Physiology & Biophysics (K.D.N., M.A.M.), Vanderbilt University School of Medicine, Nashville, Tenn, and Department of Cell Biology and Anatomy (A.W.), Medical University of South Carolina, SC.
  • Mark E. Anderson
    From the Departments of Medicine (S.K., T.Y., M.E.A., M.A.M., D.M.R.), Pharmacology (S.K., T.Y., M.E.A., D.M.R.), and Molecular Physiology & Biophysics (K.D.N., M.A.M.), Vanderbilt University School of Medicine, Nashville, Tenn, and Department of Cell Biology and Anatomy (A.W.), Medical University of South Carolina, SC.
  • Andy Wessels
    From the Departments of Medicine (S.K., T.Y., M.E.A., M.A.M., D.M.R.), Pharmacology (S.K., T.Y., M.E.A., D.M.R.), and Molecular Physiology & Biophysics (K.D.N., M.A.M.), Vanderbilt University School of Medicine, Nashville, Tenn, and Department of Cell Biology and Anatomy (A.W.), Medical University of South Carolina, SC.
  • Kevin D. Niswender
    From the Departments of Medicine (S.K., T.Y., M.E.A., M.A.M., D.M.R.), Pharmacology (S.K., T.Y., M.E.A., D.M.R.), and Molecular Physiology & Biophysics (K.D.N., M.A.M.), Vanderbilt University School of Medicine, Nashville, Tenn, and Department of Cell Biology and Anatomy (A.W.), Medical University of South Carolina, SC.
  • Mark A. Magnuson
    From the Departments of Medicine (S.K., T.Y., M.E.A., M.A.M., D.M.R.), Pharmacology (S.K., T.Y., M.E.A., D.M.R.), and Molecular Physiology & Biophysics (K.D.N., M.A.M.), Vanderbilt University School of Medicine, Nashville, Tenn, and Department of Cell Biology and Anatomy (A.W.), Medical University of South Carolina, SC.
  • Dan M. Roden
    From the Departments of Medicine (S.K., T.Y., M.E.A., M.A.M., D.M.R.), Pharmacology (S.K., T.Y., M.E.A., D.M.R.), and Molecular Physiology & Biophysics (K.D.N., M.A.M.), Vanderbilt University School of Medicine, Nashville, Tenn, and Department of Cell Biology and Anatomy (A.W.), Medical University of South Carolina, SC.

説明

<jats:p> <jats:italic>Abstract</jats:italic> —The <jats:italic>minK</jats:italic> gene encodes a 129-amino acid peptide the expression of which modulates function of cardiac delayed rectifier currents ( <jats:italic>I</jats:italic> <jats:sub>Kr</jats:sub> and <jats:italic>I</jats:italic> <jats:sub>Ks</jats:sub> ), and mutations in <jats:italic>minK</jats:italic> are now recognized as one cause of the congenital long-QT syndrome. We have generated <jats:italic>minK-</jats:italic> deficient mice in which the bacterial <jats:italic>lacZ</jats:italic> gene has been substituted for the <jats:italic>minK</jats:italic> coding region such that β-galactosidase expression is controlled by endogenous <jats:italic>minK</jats:italic> regulatory elements. In cardiac myocytes isolated from wild-type neonatal mice, <jats:italic>I</jats:italic> <jats:sub>Ks</jats:sub> is rarely recorded, while <jats:italic>I</jats:italic> <jats:sub>Kr</jats:sub> is common. In <jats:italic>minK</jats:italic> (–/–) myocytes, <jats:italic>I</jats:italic> <jats:sub>Ks</jats:sub> is absent and <jats:italic>I</jats:italic> <jats:sub>Kr</jats:sub> is significantly reduced and its deactivation slowed; these results further support a role for <jats:italic>minK</jats:italic> in modulating both <jats:italic>I</jats:italic> <jats:sub>Ks</jats:sub> and <jats:italic>I</jats:italic> <jats:sub>Kr</jats:sub> . Despite these changes, ECGs in (+/+) and (–/–) animals are no different at adult and at neonatal stages. ECG responses to isoproterenol are also similar in the 2 groups. β-Galactosidase staining in postnatal <jats:italic>minK</jats:italic> (–/–) hearts is highly restricted, to the sinus-node region, caudal atrial septum, and proximal conducting system. Moreover, as early as embryonal day 11, segmentally restricted β-galactosidase expression is observed in the portions of the sinoatrial and atrioventricular junctions that are thought to give rise to the conducting system, thereby implicating <jats:italic>minK</jats:italic> expression as an early event in conduction system development. More generally, the restricted nature of <jats:italic>minK</jats:italic> expression in the mouse heart suggests species-specific roles of this gene product in mediating the electrophysiological properties of the heart. </jats:p>

収録刊行物

  • Circulation Research

    Circulation Research 84 (2), 146-152, 1999-02-05

    Ovid Technologies (Wolters Kluwer Health)

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