|[Frontiers in Bioscience 2, d298-308, June 15, 1997]|
TRANSGENIC RABBIT MODELS FOR THE STUDY OF ATHEROSCLEROSIS
John M. Taylor and Jianglin Fan
Gladstone Institute of Cardiovascular Disease, the Department of Physiology, and the Cardiovascular Research Institute, University of California, San Francisco, CA
A cDNA encoding rabbit APOBEC-1 in a liver-specific expression vector was used to generate transgenic rabbits (51). The corresponding protein is an editing factor for apoB100 mRNA that deaminates a specific cytidine at residue 6666 to yield uridine: editing changes a glutamine codon (CAA) to a translation stop codon (UAA) resulting in the B48 form of the apolipoprotein. The editing factor is found in the intestine but not in the liver of the nontransgenic rabbit, making this animal species a superb model to investigate the role of apoB editing in lipoprotein metabolism. The transgenic rabbits had significant decreases in VLDL, IDL, and LDL accompanied by an increase in HDL. The most striking effect of liver-specific APOBEC-1 expression was the induction of hepatocellular carcinoma and liver displasia in the transgenic rabbits. These observations demonstrated that other mRNAs besides apoB100 can be edited and that aberrant editing of hepatic mRNAs can alter cell growth and contribute to tumorigenesis (52).