Studies of Apolipoprotein B And Lipoprotein(a) in Transgenic Mice

Abstract

Two of the many differences in lipoprotein metabolism between mice and humans are a predominance of high density lipoproteins (HDL) in mice compared with high levels of low density lipoproteins (LDL) in humans, and the lack of either apolipoprotein(a) (apo[a]) or lipoprotein(a) (Lp[a]) in the mouse. In order to develop a strain of mice with higher levels of LDL and with Lp(a), a Pl phagemid library was screened for a human apoB genomic clone. A clone containing the entire human apoB gene was isolated and used to create multiple lines of mice expressing high levels of human apoB. The lipoproteins of the human apoB transgenic animals differed from control mice due to the presence of significant amounts of low-density lipoprotein particles containing human apoB1. The human apoB transgenic mice were crossed with a previously described line of transgenic mice expressing human apo(a) cDNA2. The resulting combined transgenic animals expressing both human apoB and human apo(a) produced an Lp(a) particle sharing many properties with Lp(a) present in the plasma of humans. The present series of transgenic animals will serve as useful substrates to address issues relevant to LDL and Lp(a) that are difficult to approach in either humans or naturally occurring animal models.