Vascular endothelium-specific overexpression of human catalase in cloned pigs

Transgenic Res. 2011 Oct;20(5):989-1001. doi: 10.1007/s11248-010-9473-7. Epub 2010 Dec 18.


The objective of this study was to develop transgenic Yucatan minipigs that overexpress human catalase (hCat) in an endothelial-specific manner. Catalase metabolizes hydrogen peroxide (H(2)O(2)), an important regulator of vascular tone that contributes to diseases such as atherosclerosis and preeclampsia. A large animal model to study reduced endothelium-derived H(2)O(2) would therefore generate valuable translational data on vascular regulation in health and disease. Yucatan minipig fetal fibroblasts stably co-transfected with human catalase (Tie2-hCat) and eGFP expression constructs were isolated into single-cell populations. The presence of the Tie2-hCat transgene in individual colonies of fibroblasts was determined by PCR. Transgenic fibroblasts were used for nuclear transfer into enucleated oocytes by electrofusion. A minimum of 140 cloned embryos were transferred per surrogate sow (n = 4). All four surrogates maintained pregnancies and piglets were delivered by cesarean section. Nine male piglets from three of the four litters carried the Tie2-hCat transgene. Expression of human catalase mRNA and overall elevated catalase protein in isolated umbilical endothelial cells from transgenic piglets were verified by RT-PCR and western blot, respectively, and endothelial localization was confirmed by immunohistochemistry. Increased enzymatic activity of catalase in transgenic versus wild-type endothelial cells was inferred based on significantly reduced levels of H(2)O(2) in culture. The similarities in swine and human cardiovascular anatomy and physiology will make this pig model a valuable source of information on the putative role of endothelium-derived H(2)O(2) in vasodilation and in the mechanisms underlying vascular health and disease.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cardiovascular Diseases / enzymology
  • Cardiovascular Diseases / genetics
  • Catalase / genetics*
  • Catalase / metabolism
  • Cloning, Organism*
  • Disease Models, Animal
  • Embryo Transfer
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism
  • Female
  • Gene Expression
  • Humans
  • Hydrogen Peroxide / metabolism*
  • Male
  • Pregnancy
  • Receptor, TIE-2 / genetics
  • Swine
  • Swine, Miniature / genetics*
  • Swine, Miniature / metabolism


  • Hydrogen Peroxide
  • Catalase
  • Receptor, TIE-2