Conservation of an AE3 Cl-/HCO3- exchanger cardiac-specific exon and promoter region and AE3 mRNA expression patterns in murine and human hearts

Abstract

A cardiac-specific variant of the rat AE3 Cl-/HCO3- exchanger mRNA is transcribed from a promoter located in the sixth intron of a larger transcription unit expressed in brain and other tissues. The cardiac mRNA contains an alternative first exon encoding a 73-amino acid NH2-terminal sequence that replaces the first 270 amino acids of the brain AE3 variant. The present study was conducted to determine whether the cardiac-specific promoter region and exon are conserved in other species and to examine the expression patterns of AE3 mRNAs in adult tissues and during development. Analysis of murine and human genomic clones showed that both contain counterparts of the rat alternative exon. The cardiac promoter region is highly conserved in all three species and contains several potential transcription factor binding sites, including consensus MCAT and E-box sequences. Tissue-specific and developmental patterns of AE3 gene expression were examined by Northern blot hybridization. Mouse and human, like the rat, express both the 3.6-kb cardiac-specific AE3 mRNA and a 4.4-kb AE3 transcript found in brain, heart, and other tissues. Levels of the cardiac-specific transcript in mouse heart increase 17-fold between the fetal and adult stages, while the amount of the longer AE3 mRNA in heart decreases substantially. Furthermore, although the cardiac-specific mRNA is expressed in both atria and ventricles of mouse heart, the longer transcript is confined to the atria. These results suggest that the two AE3 variants have distinct roles in cardiac function and that the mechanisms regulating their expression are different.