Molecular characterization and acute phase expression of the multiple Mus caroli alpha 1-acid glycoprotein (AGP) genes. Differences in glucocorticoid stimulation and regulatory elements between the rat and mouse AGP genes.

Abstract

In this study, we have analyzed alpha 1-acid glycoprotein (AGP) production in the wild mouse strain Mus caroli to assess whether the stimulation of AGP by inflammatory mediators has been conserved during rodent evolution and to determine what DNA elements manifested the hormonal induction in mouse AGP gene sequences. To this end, we isolated the M. caroli AGP genes and characterized their expression. Southern blot hybridization of M. caroli genomic DNA revealed the existence of approximately eight genes per haploid genome, and eight distinct genes were identified from a M. caroli lambda genomic DNA library. Two actively transcribed and acute phase-regulated genes (AGP genes 1 and 8) were identified by sequence correlation with the two different cDNAs isolated from an acute phase liver cDNA library. Two-dimensional gel analysis of in vitro transcription and translation products from these two cDNAs displayed a pattern of protein precursors identical with that shown by in vitro translation of the endogenous AGP mRNA. A glucocorticoid-responsive element (GRE) in M. caroli AGP gene 8 was localized to a unique sequence distal to the relative position of the rat AGP gene GRE. The mouse region analogous to the rat GRE did not show glucocorticoid-mediated induction of an indicator gene although greater than 90% sequence similarity is maintained. GRE function in this mouse region was improved by introducing a point mutation that restores the rat AGP GRE consensus sequence, although the relative induction obtained was less than the wild-type rat AGP GRE.