Expression of human apolipoprotein B100 in transgenic mice. Editing of human apolipoprotein B100 mRNA

Apolipoprotein B (apoB) is a large glycoprotein that circulates in plasma as a major constituent of numerous lipoproteins. ApoB exists in two forms: apoB48 and apoB100. ApoB48 is identical in sequence to the N-terminal region of apoB100 and is generated by sequence-specific mRNA editing of the apoB100 transcript. Here, we describe the development of a line of mice expressing a human apoB transgene driven by promoter/enhancer sequences from the transthyretin gene. In these mice, immunodetectable human apoB100 is synthesized by the liver, kidney, and brain. Human apoB100 is found in low concentration (approximately 0.1 mg/dl) in the plasma of the transgenic mice and circulates in the low density lipoprotein fraction. The hepatic human apoB100 transcripts undergo mRNA editing at only slightly lower efficiency than the endogenous mouse apoB100 message. Therefore, there is no absolute species specificity to the apoB100 mRNA editing process.