Chromosomal location of the murine anion exchanger genes encoding AE2 and AE3

Chloride/bicarbonate exchange is present or excitable in nearly all cell types in which it has been sought. The prototype chloride/bicarbonate exchange protein is the anion exchange protein band 3 (otherwise known as anion exchanger 1 or AE1) of the red cell membrane. Anion exchanger 1 serves to increase the CO sub(2)-carrying capacity of the blood while also anchoring the red cell cytoskeleton to its plasma membrane. Two additional anion exchanger or band 3-related genes and their products have been characterized in the mouse. The anion exchanger 2, AE2 and anion exchanger 3, AE3 proteins encoded by these genes mediate chloride/bicarbonate exchange and are postulated to contribute to regulated cellular homeostasis of pH sub(i), [Cl super(-)], and volume. In general, the proteins of the anion exchange family (AE1, AE2, AE3) are composed of two regions representing an intramembrane domain and a cytoplasmic domain. The intramembrane domains of AE2 and AE3, which is responsible for anion exchange, are conserved, but the cytoplasmic domains have diverged from AE1. In the case of AE1, the cytoplasmic domain contains binding sites for ankyrin, band 4.1, band 4.2, hemoglobin, and glyceraldehyde-3-phosphate. However, the functions of the cytoplasmic domains of AE2 and AE3 are unknown. Tissue distributions of the expression of AE2 and AE3 are different: AE2 is widely distributed, but AE3 is found mostly in neural tissues. The gene for murine erythrocyte membrane protein band 3 (gene symbol Embp3), also known as AE1, maps to Chromosome (Chr) 11, while the human AE1 homolog, erythrocyte protein band 3 (gene symbol EPB3) maps to Chr 17. The nomenclature in the human has been altered to reflect the multiplicity of anion exchangers; EPB3 is now AE1. In order to maintain consistency, a similar change has been approved for the mouse by the International Mouse Nomenclature Committee. The mouse gene symbols will henceforth be Ae1, Ae2, and Ae3, and so forth in the order of their discovery. We have mapped the murine anion exchanger genes, Ae2 and Ae3, to determine whether these genes co-localize with each other or with mutations for which they might be deemed as candidate genes. Human AE2 has been assigned to Chr 7q35-q36. The linkage map of human Chr 7 exhibits extensive homology with mouse Chr 5 and 6. This homology is particularly striking for loci on 7q. However, the regions of homology are not continuous. Instead, as is well established, rearrangements have occurred dur