Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells

Cell. 1992 Oct 16;71(2):343-53. doi: 10.1016/0092-8674(92)90362-g.


apoE-deficient mice have been created by homologous recombination in ES cells. On a low fat, low cholesterol chow diet these animals have plasma cholesterol levels of 494 mg/dl compared with 60 mg/dl in control animals, and when challenged with a high fat Western-type diet, these animals have plasma cholesterol levels of 1821 mg/dl compared with 132 mg/dl in controls. This marked hypercholesterolemia is primarily due to elevated levels of very low and intermediate density lipoproteins. At 10 weeks of age, apoE-deficient mice have already developed atherosclerotic lesions in the aorta and coronary and pulmonary arteries. apoE-deficient mice are a promising small animal model to help understand the role of apoE in vivo and the genetic and environmental determinants of atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aorta / pathology
  • Apolipoproteins E / deficiency*
  • Arteriosclerosis / genetics*
  • Arteriosclerosis / pathology
  • Cholesterol / blood
  • Coronary Vessels / pathology
  • Disease Models, Animal
  • Hypercholesterolemia / genetics*
  • Hypercholesterolemia / pathology
  • Lipoproteins / blood
  • Lipoproteins, IDL
  • Lipoproteins, VLDL / blood
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Pulmonary Artery / pathology
  • Stem Cells


  • Apolipoproteins E
  • Lipoproteins
  • Lipoproteins, IDL
  • Lipoproteins, VLDL
  • Cholesterol