The repertoire of Na,K-ATPase alpha and beta subunit genes expressed in the zebrafish, Danio rerio

We have identified a cohort of zebrafish expressed sequence rags encoding e ight Na,K-ATPase alpha subunits and Five beta subunits. Sequence comparison s and phylogenetic analysis indicate that five of the zebrafish a subunit g enes comprise an alpha1-like gene subfamily and two are orthologs of the ma mmalian alpha3 subunit gene. The remaining a subunit clone is most similar to the mammalian alpha2 subunit. Among the Five beta subunit genes, two are orthologs of the mammalian beta1 isoform, one represents a beta2 ortholog, and two are orthologous to the mammalian beta3 subunit. Using zebrafish ra diation hybrid and meiotic mapping panels, we determined linkage assignment s for each or and beta subunit gene. Na,K-ATPase genes are dispersed in the zebrafish genome with the exception of Four of the alpha1-like genes, whic h are tightly clustered on linkage group 1. Comparative mapping studies ind icate that most of the zebrafish Na,K-ATPase genes localize to regions of c onserved synteny between zebrafish and humans. The expression patterns of N a,K-ATPase alpha and beta subunit genes in zebrafish are quite distinctive. No two alpha or beta subunit genes exhibit the same expression profile. To gether, our data imply a very high degree of Na,K-ATPase isoenzyme heteroge neity in zebrafish, with the potential for 40 structurally distinct alpha/b eta subunit combinations. Differences in expression patterns of alpha and b eta 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 relationshi ps for sodium pump isoforms using reverse genetic approaches.