Inhibition of intimal lipid deposition in human apolipoprotein A1 transgenic mice.
1. Southern blot confirmed the emergence of the human apolipoprotein A1 (h-apoA1) gene (four to 15 copies) in newborn transgenic mice. The inheritance pattern of h-apoA1 transgene in three generations of progeny was compatible with a single autosomal integration site. 2. Northern blot showed h-apoA1 mRNA expressed mainly in liver, kidney and aorta. The total plasma apoA1 (murine plus human) level was significantly increased to 58 and 118 in transgenic mice without or under zinc induction, respectively. The majority was h-apoA1. Plasma lecithin:cholesterol acyltransferase activity was positively correlated with h-apoA1 levels in transgenic mice (r = 0.43; P < 0.01). 3. After a high cholesterol intake for 14 weeks, the incidence of fatty streak at the aortic sinus was 40% in transgenic mice and 80% in controls. Expression of platelet-derived growth factor-B, c-myc and c-fos proteins was much weaker in smooth muscle cells at the aortic sinus in transgenic mice.
She
M
M
Department of Pathology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. shemp@public.bta.net.ch
Li
H
H
Yu
L
L
Gu
S
S
Wang
Z
Z
D000818:Animals; D001011:Aorta / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D015139:Blotting, Southern; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007421:Intestine, Small / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D050356:Lipid Metabolism; D008055:Lipids / Q000037:antagonists & inhibitors* / Q000097:blood; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017539:Tunica Intima / Q000378:metabolism*
D016632:Apolipoprotein A-I; D008055:Lipids; D012333:RNA, Messenger; D002784:Cholesterol