Selenoprotein expression is essential in endothelial cell development and cardiac muscle function

Rajeev K. Shrimali, James A. Weaver, Georgina F. Miller, Matthew F. Starost, Bradley A. Carlson, Sergey V. Novoselov, Easwari Kumaraswamy, Vadim N. Gladyshev, Dolph L. Hatfield

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

LoxP-Cre technology was used to remove the selenocysteine tRNA gene, trsp, in either endothelial cells or myocytes of skeletal and heart muscle to elucidate the role of selenoproteins in cardiovascular disease. Loss of selenoprotein expression in endothelial cells was embryonic lethal. A 14.5-day-old embryo had numerous abnormalities including necrosis of the central nervous system, subcutaneous hemorrhage and erythrocyte immaturity. Loss of selenoprotein expression in myocytes manifested no apparent phenotype until about day 12 after birth. Affected mice had decreased mobility and an increased respiratory rate, which proceeded rapidly to death. Pathological analysis revealed that mice lacking trsp had moderate to severe myocarditis with inflammation extending into the mediastinitis. Thus, ablation of selenoprotein expression demonstrated an essential role of selenoproteins in endothelial cell development and in proper cardiac muscle function. The data suggest a direct connection between the loss of selenoprotein expression in these cell types and cardiovascular disease.

Original languageEnglish (US)
Pages (from-to)135-142
Number of pages8
JournalNeuromuscular Disorders
Volume17
Issue number2
DOIs
StatePublished - Feb 2007

Keywords

  • Cardiovascular disease
  • Conditional knockout
  • Endothelial cells
  • Heart muscle
  • Selenocysteine
  • Selenocysteine tRNA
  • Selenoproteins

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Neurology
  • Clinical Neurology
  • Genetics(clinical)

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