Regulation of the metabolism of plasma lipoproteins by apolipoprotein A-II.

Mouse apolipoprotein (apo) A-II has three variants (type A, B, and C) among inbred strains. To clarify the role of ApoA-II in the metabolism of high density lipoproteins (HDL), we constructed a new congenic mouse strain (P1.R1-Apoa2b) with type B ApoA-II of the SAMR1 strain on the genetic background of the SAMP1 strain, and examined it together with another ApoA-II congenic strain (R1.P1-Apoa2c) containing type C ApoA-II of the SAMPI strain on the SAMR1 strain and the parental SAMP1 and SAMR1 strains. Genetic characterization of the congenic strains indicated that only small regions surrounding the ApoA-II gene of the parental strains had been transferred. The strains with Apoa2c had lower plasma concentrations of HDL and ApoA-II, and a smaller HDL particle size than strains with Apoa2b. We detected no significant differences in the mRNA levels of ApoA-II or in the in vitro translational efficiency of the ApoA-II mRNA among the four strains. These findings suggested that the differences in the post-translational modification or efficiency of secretion between the Apoa2b and Apoa2c protein regulates the ApoA-II concentration which in turn determines the concentration and size of HDL in mice.