High level expression of human apolipoprotein A-I in transgenic rats raises total serum high density lipoprotein cholesterol and lowers rat apolipoprotein A-I

• Published in: Transgenic research Vol. 1; no. 3; pp. 142 - 147
• Main Authors: Swanson, M E, Hughes, T E, Denny, I S, France, D S, Paterniti, Jr, J R, Tapparelli, C, Gfeller, P, Bürki, K
• Format: Journal Article
• Language: English
• Published: Netherlands 01-05-1992
• Subjects: Animals; Animals, Genetically Modified; Apolipoprotein A-I - biosynthesis; Apolipoprotein A-I - genetics; Apolipoprotein A-I - metabolism; Blotting, Western; Cholesterol - blood; Cholesterol, HDL - blood; Female; Gene Expression; Homozygote; Humans; Lipoproteins - blood; Male; Organ Specificity; Phospholipids - blood; Rats; Rats, Inbred Strains; Restriction Mapping; RNA, Messenger - genetics; RNA, Messenger - metabolism
• ISSN: 0962-8819; 1573-9368
• DOI: 10.1007/bf02528779

To examine the consequences of increased apolipoprotein A-I production on cholesterol and lipoprotein metabolism, we have produced two lines of transgenic rats; one expressing moderate and one very high levels of human apolipoprotein A-I. The rats were produced by microinjection of a 13 kbp DNA fragment containing the human apolipoprotein A-I gene plus 10 kbp of its 5' flanking sequence and 1 kbp of its 3' flanking sequence. Both lines of transgenic rats express human apolipoprotein A-I mRNA in liver and human apolipoprotein A-I in plasma. Sera from these rats contain significantly higher levels of total apolipoprotein A-I, high density lipoprotein cholesterol and phospholipid than sera from non-transgenic littermates. Transgenic rats expressing high levels of human apolipoprotein A-I have reduced levels of serum rat apolipoprotein A-I suggesting a mechanism exists to down-regulate apolipoprotein A-I production. These transgenic rats provide a unique animal model to examine the effects of increased apolipoprotein A-I production on lipid and lipoprotein metabolism.