High level expression of human apolipoprotein A-I in transgenic rats raises total serum high density lipoprotein cholesterol and lowers rat apolipoprotein A-I.
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.
Swanson
M E
ME
Department of Molecular Biology, Sandoz Research Institute, East Hanover, NJ 07936.
Hughes
T E
TE
Denny
I S
IS
France
D S
DS
Paterniti
J R
JR
Tapparelli
C
C
Gfeller
P
P
Bürki
K
K
D000818:Animals; D030801:Animals, Genetically Modified; D016632:Apolipoprotein A-I / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D015153:Blotting, Western; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D015870:Gene Expression; D006720:Homozygote; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D009928:Organ Specificity; D010743:Phospholipids / Q000097:blood; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D015183:Restriction Mapping
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D008074:Lipoproteins; D010743:Phospholipids; D012333:RNA, Messenger; D002784:Cholesterol