Immune-type receptor genes in zebrafish share genetic and functional properties with genes encoded by the mammalian leukocyte receptor cluster

An extensive, highly diversified multigene family of novel immunetype recep tor (nitr) genes has been defined in Danio rerio (zebrafish), The genes are predicted to encode type I transmembrane glycoproteins consisting of extra cellular variable (V) and V-like C2 (V/C2) domains, a transmembrane region and a cytoplasmic tail. All of the genes examined encode immunoreceptor tyr osine-based inhibition motifs in the cytoplasmic tail. Radiation hybrid pan el mapping and analysis of a deletion mutant line (b240) indicate that a mi nimum of approximate to 40 nitr genes are contiguous in the genome and span approximate to0.6 Mb near the top of zebrafish linkage group 7, One flanki ng region of the nitr gene complex shares conserved synteny with a region o f mouse chromosome 7. which shares conserved synteny with human 19q13.3-q13 .4 that encodes the leukocyte receptor cluster. Antibody-induced crosslinki ng of Nitrs that have been introduced into a human natural killer cell line inhibits the phosphorylation of mitogen-activated protein kinase that is t riggered by natural killer-sensitive tumor target cells, Nitrs likely repre sent intermediates in the evolution of the leukocyte receptor cluster.