Molecular analyses have resulted in the isolation of two chicken stomach AE2 anion exchanger cDNAs, AE2-1 and AE2-2. The ϳ4.3-kilobase (kb) AE2-1 cDNA contains an open reading frame that encodes a predicted polypeptide of ϳ135 kDa that is homologous to AE2 anion exchangers from other species. The partial ϳ1.7-kb AE2-2 cDNA, which differs from the AE2-1 cDNA in two regions, would be predicted to encode an AE2 polypeptide with an alternative N-terminal cytoplasmic tail. Examination of the distribution of these variant transcripts has revealed that AE2 transcripts ranging in size from ϳ4.4 to ϳ7.3 kb accumulate in various adult tissues. However, in the stomach, the unique sequence at the 5-end of AE2-1 is preferentially associated with transcripts that range in size from ϳ4.5 to ϳ4.9 kb, while the unique sequence at the 5-end of AE2-2 is preferentially associated with the ϳ7.3-kb AE2 RNA species. In situ hybridization analyses have further revealed that AE2 transcripts accumulate to very high levels within the acid-secreting epithelial cells of the profound gland in the stomach and, to a lesser extent, within the mucussecreting cells of the superficial gland that line the stomach lumen. This result suggests that AE2 anion exchangers are involved in the regulation of intracellular pH in each of these gastric epithelial cell types.Plasma membrane electroneutral anion exchangers are involved in the regulation of intracellular pH (1) and cell volume (2). The best characterized anion exchanger is the erythroid AE1 anion exchanger (band 3 protein), which primarily mediates the one-for-one exchange of bicarbonate for chloride (3). Molecular studies have indicated that variant AE1 anion exchangers are encoded by the AE1 gene in mouse (4), rat (5), human (6), and chicken (7-9). These variant AE1 transcripts differ only at their 5Ј-ends and encode polypeptides with alternative N-terminal cytoplasmic domains. These molecular analyses coupled with immunolocalization studies (10, 11) have suggested that specific AE1 variants mediate the electroneutral anion exchange activity that has been localized to the basolateral membrane of the acid-secreting A-intercalated cells of the kidney collecting duct.Electroneutral anion exchange activities have also been characterized in a variety of other cell types, including gastric parietal cells (12), cardiac Purkinje fibers (13), and renal mesangial cells (14,15). The genes that encode most of these anion exchange activities are not known. However, immunolocalization studies using AE2 anion exchanger-specific peptide antibodies have suggested that the AE2 anion exchanger mediates the basolateral chloride/bicarbonate exchange activity of the acid-secreting parietal cells of the mammalian stomach (16). The studies described here have revealed that variant chicken AE2 anion exchanger transcripts are generated by a complex pattern of alternative transcriptional initiation and differential RNA splicing. These transcripts are expressed in a wide variety of tissues including the proventriculus, th...