Replacement by homologous recombination of the minK gene with lacZ reveals restriction of minK expression to the mouse cardiac conduction system

Sabina Kupershmidt, Tao Yang, Mark E. Anderson, Andy Wessels, Kevin D. Niswender, Mark A. Magnuson, Dan M. Roden

Research output: Contribution to journalArticlepeer-review

Abstract

The mink gene encodes a 129-amino acid peptide the expression of which modulates function of cardiac delayed rectifier currents (I(Kr) and I(Ks)), and mutations in mink are now recognized as one cause of the congenital long- QT syndrome. We have generated minK-deficient mice in which the bacterial lacZ gene has been substituted for the mink coding region such that β- galactosidase expression is controlled by endogenous mink regulatory elements. In cardiac myocytes isolated from wild-type neonatal mice, I(Ks) is rarely recorded, while I(Kr) is common. In mink (-/-) myocytes, I(Ks) is absent and I(Kr) is significantly reduced and its deactivation slowed; these results further support a role for mink in modulating both I(Ks) and I(Kr). 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 mink (-/-) 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 mink expression as an early event in conduction system development. More generally, the restricted nature of mink expression in the mouse heart suggests species-specific roles of this gene product in mediating the electrophysiological properties of the heart.

Original languageEnglish (US)
Pages (from-to)146-152
Number of pages7
JournalCirculation research
Volume84
Issue number2
DOIs
StatePublished - Feb 5 1999
Externally publishedYes

Keywords

  • Conducting system
  • Delayed rectifier
  • Development
  • K current

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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