Apolipoprotein(a) (Apo(a)) glycoprotein isoforms result from size differences in Apo(a) mRNA in baboons

Abstract

Like humans, baboons possess serum lipoprotein(a) that contains apolipoprotein(a) (apo(a], and baboon apo(a) also occurs in distinguishable glycoprotein isoforms. To investigate the molecular basis for isoform size variation, we isolated hepatic RNA from baboons possessing different apo(a) isoforms for Northern blot analyses with rhesus apo(a) cDNA probes. In a survey of 22 baboons, we detected a variety of sizes of apo(a) transcripts (5.2-11.2 kilobases) that corresponded with relative mobilities and numbers of serum apo(a) isoforms. In unrelated baboons possessing apo(a) isoforms of similar mobilities, we detected apo(a) transcripts with similar mobilities. In related baboons possessing apo(a) isoforms that were identical by descent, apo(a) transcripts were also identical in size. Using data from 22 baboons included in this study, we compared the sizes of 20 apo(a) isoforms and corresponding transcripts. Linear regression analysis established a highly significant correlation (p less than 0.001) between estimated apo(a) transcript size and glycoprotein mass (r2 = 0.996). From these results, we conclude that apo(a) glycoprotein isoforms are due to structural differences in apo(a) transcripts. However, we also noted exceptions to correspondence between apo(a) transcripts and isoforms that suggest the action of additional post-transcriptional control of serum apo(a) levels.