Pathophysiology of apolipoprotein E deficiency in mice: relevance to apo E-related disorders in humans

FASEB J. 2001 Dec;15(14):2623-30. doi: 10.1096/fj.01-0463com.


Apolipoprotein E (apo E) deficiency (or its abnormalities in humans) is associated with a series of pathological conditions including dyslipidemia, atherosclerosis, Alzheimer's disease, and shorter life span. The purpose of this study was to characterize these conditions in apo E-deficient C57BL/6J mice and relate them to human disorders. Deletion of apo E gene in mice is associated with changes in lipoprotein metabolism [plasma total cholesterol (TC) (>+400%), HDL cholesterol (-80%), HDL/TC, and HDL/LDL ratios (-93% and -96%, respectively), esterification rate in apo B-depleted plasma (+100%), plasma triglyceride (+200%), hepatic HMG-CoA reductase activity (-50%), hepatic cholesterol content (+30%)], decreased plasma homocyst(e)ine and glucose levels, and severe atherosclerosis and cutaneous xanthomatosis. Hepatic and lipoprotein lipase activities, hepatic LDL receptor function, and organ antioxidant capacity remain unchanged. Several histological/immunohistological stainings failed to detect potential markers for neurodegenerative disease in the brain of 37-wk-old male apo E-KO mice. Apo E-KO mice may have normal growth and development, but advanced atherosclerosis and xanthomatosis may indirectly reduce their life span. Apo E plays a crucial role in regulation of lipid metabolism and atherogenesis without affecting lipase activities, endogenous antioxidant capacity, or appearance of neurodegenerative markers in 37-wk-old male mice.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Apolipoproteins E / deficiency*
  • Apolipoproteins E / genetics
  • Blood Glucose / metabolism
  • Body Weight / physiology
  • Brain / metabolism
  • Cholesterol / metabolism
  • Esterification
  • Genotype
  • Glial Fibrillary Acidic Protein / analysis
  • Homocysteine / blood
  • Humans
  • Hydroxymethylglutaryl CoA Reductases / metabolism
  • Hyperlipidemias / blood
  • Hyperlipidemias / physiopathology
  • Immunohistochemistry
  • Kidney / metabolism
  • Lipase / blood
  • Lipids / blood
  • Lipoproteins, HDL / metabolism
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurofilament Proteins / analysis
  • Receptors, LDL / physiology
  • Survival Analysis
  • Time Factors
  • Tissue Distribution


  • Antioxidants
  • Apolipoproteins E
  • Blood Glucose
  • Glial Fibrillary Acidic Protein
  • Lipids
  • Lipoproteins, HDL
  • Neurofilament Proteins
  • Receptors, LDL
  • Homocysteine
  • Cholesterol
  • Hydroxymethylglutaryl CoA Reductases
  • Lipase