Cardiomyopathy in α-kinase 3 (Alpk3)-deficient mice

I. Van Sligtenhorst, Z. M. Ding, Zheng-Zheng Shi, R. W. Read, G. Hansen, Peter Vogel

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Cardiomyopathy developed in mice deficient for α-kinase 3 (ALPK3), a nuclear kinase previously implicated in the differentiation of cardiomyocytes. Alpk3-/- mice were produced according to normal Mendelian ratios and appeared normal except for a nonprogressive cardiomyopathy that had features of both hypertrophic and dilated forms of cardiomyopathy. Cardiac hypertrophy in Alpk3-/- mice was characterized by increased thickness of both left and right ventricular (LV and RV) walls and by markedly increased heart weight and increased heart weight/body weight and heart weight/tibia length ratios. Magnetic resonance imaging studies confirmed the increased thickness in both septal and LV free walls at end-diastole, although there was no significant change in LV wall thickness at end-systole. Myocardial hypertrophy was the predominant feature in Alpk3-/- mice, but several changes more typically associated with dilated cardiomyopathy included a marked increase in end-diastolic and end-systolic LV volume, as well as reduced cardiac output, stroke volume, and ejection fractions, suggesting LV chamber dilation. Magnetic resonance imaging showed a 50% reduction in both septal and free wall LV contractility in Alpk3-/- mice. Interstitial fibrosis and inflammation were notably absent in Alpk3-/- mice; however, light and electron microscopy revealed altered cardiomyocyte architecture, characterized by reduced numbers of abnormal intercalated discs being associated with mild disarray of myofibrils. These lesions could account for the impaired contractility of the myofibrillar apparatus and contribute to the pathogenesis of cardiomyopathy in Alpk3-/- mice.

Original languageEnglish (US)
Pages (from-to)131-141
Number of pages11
JournalVeterinary Pathology
Volume49
Issue number1
DOIs
StatePublished - Jan 1 2012

Keywords

  • α-kinase 3
  • cardiomyopathy
  • heart failure
  • intercalated discs
  • knockout mice

ASJC Scopus subject areas

  • veterinary(all)

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