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 compatibl e 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 i ncreased to 58 and 118 in transgenic mice without or under zinc induction, respectively. The majority was h-apoA1. Plasma lecithin:cholesterol acyltra nsferase activity was positively correlated with h-apoA1 levels in transgen ic mice (r = 0.43; P < 0.01). 3. After a high cholesterol intake for 14 weeks, the incidence of fatty str eak at the aortic sinus was 40% in transgenic mice and 80% in controls. Exp ression of platelet-derived growth factor-B, c-myc and c-fos proteins was m uch weaker in smooth muscle cells at the aortic sinus in transgenic mice.