Hepatic expression of the catalytic subunit of the apolipoprotein B mRNA editing enzyme (apobec-1) ameliorates hypercholesterolemia in LDL receptor-deficient rabbits

Hum Gene Ther. 1996 May 20;7(8):943-57. doi: 10.1089/hum.1996.7.8-943.


Apolipoprotein (apo) B48, a protein contained in intestinally derived lipoprotein particles, is synthesized by post-transcriptional editing of apoB100 mRNA. This reaction is mediated by an enzyme complex that includes the catalytic subunit, apobec-1. The liver of most mammals, by contrast, contains only unedited apoB mRNA and secretes apoB100, the major protein component of plasma low-density lipoprotein (LDL). Because rabbits, like humans, fail to edit hepatic apoB100 mRNA, we introduced a recombinant adenovirus encoding apobec-1 into the livers of LDL receptor-defective rabbits to determine the impact on lipoprotein metabolism of hepatic apoB48 secretion. Transgene expression was mainly confined to the liver and was sustained for up to 3 weeks following virus administration, as evidenced by the presence of apobec-1 mRNA and the ability of hepatic S100 extracts to edit a synthetic apoB RNA template in vitro. The transient induction of hepatic apoB mRNA editing accompanied alterations in very-low-density lipoprotein (VLDL) size, the presence of apoB48 in fractions spanning the VLDL and LDL range, and modest reductions in total plasma cholesterol levels.

Publication types

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

MeSH terms

  • APOBEC-1 Deaminase
  • Animals
  • Apolipoproteins B / blood
  • Catalysis
  • Cholesterol / blood
  • Cytidine Deaminase / genetics*
  • Cytidine Deaminase / metabolism
  • Genetic Therapy*
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / therapy*
  • Liver / metabolism*
  • RNA Processing, Post-Transcriptional
  • Rabbits
  • Receptors, LDL / metabolism*
  • Triglycerides / blood


  • Apolipoproteins B
  • Receptors, LDL
  • Triglycerides
  • Cholesterol
  • AICDA (activation-induced cytidine deaminase)
  • APOBEC-1 Deaminase
  • APOBEC1 protein, human
  • Cytidine Deaminase