We have identified a cohort of zebrafish expressed sequence tags encoding eight Na,K-ATPase α subunits and five β subunits. Sequence comparisons and phylogenetic analysis indicate that five of the zebrafish α subunit genes comprise an α1-like gene subfamily and two are orthologs of the mammalian α3 subunit gene. The remaining α subunit clone is most similar to the mammalian α2 subunit. Among the five β subunit genes, two are orthologs of the mammalian β1 isoform, one represents a β2 ortholog, and two are orthologous to the mammalian β3 subunit. Using zebrafish radiation hybrid and meiotic mapping panels, we determined linkage assignments for each α and β subunit gene. Na,K-ATPase genes are dispersed in the zebrafish genome with the exception of four of the α1-like genes, which are tightly clustered on linkage group 1. Comparative mapping studies indicate that most of the zebrafish Na,K-ATPase genes localize to regions of conserved synteny between zebrafish and humans. The expression patterns of Na,K-ATPase α and β subunit genes in zebrafish are quite distinctive. No two α or β subunit genes exhibit the same expression profile. Together, our data imply a very high degree of Na, K-ATPase isoenzyme heterogeneity in zebrafish, with the potential for 40 structurally distinct α/β subunit combinations. Differences in expression patterns of α and β subunits suggest that many of the isoenzymes are also likely to exhibit differences in functional properties within specific cell and tissue types. Our studies form a framework for analyzing structure function relationships for sodium pump isoforms using reverse genetic approaches.
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