DIFFERENTIAL EXPRESSION OF THE MOUSE ALPHA-1-ACID GLYCOPROTEIN GENES (AGP-1 AND AGP-2) DURING INFLAMMATION AND AGING

In this study we investigated the expression of the Balb/c mouse alpha-1-acid glycoprotein genes. Mice, like humans, have two distinct alpha-1-acid glycoprotein mRNAs. As in humans and rats, mouse alpha-1-acid glycoprotein is a strong acute-phase reactant and its expression can be induced by acute-phase stimulatory agents such as bacterial lipopolysaccharides. Southern analysis and partial sequencing of different alpha-1-acid glycoprotein genomic clones indicated the existence of three distinct alpha-1-acid glycoprotein genes in the Balb/c genome. Using oligonucleotide hybridization, we showed that two of the three genes were expressed while the third gene was either not expressed or expressed at extremely low levels. The mRNA levels for the two expressed genes, alpha-1-acid glycoprotein-1 and alpha-1-acid glycoprotein-2, were both induced during the acute-phase response. However, alpha-1-acid glycoprotein-2 mRNA was present in at least 10-fold higher levels in both induced and uninduced mice. There were also differences in the development patterns of the two mRNAs in that the constitutive alpha-1-acid glycoprotein-1 mRNA levels increased 20-fold between 2 and 7 months, while alpha-1-acid glycoprotein-2 mRNA pools remained constant. During the acute-phase response in aged animals, there was an increase in the time required for both mRNAs to respond, and the maximum induced level of both mRNAs decreased. These studies set the stage for future experiments to determine the mechanisms by which the different alpha-1-acid glycoprotein genes are regulated during the acute-phase response and how aging affects these regulatory processes.