Gene structure of human and mouse NKLAM, a gene associated with cellular cytotoxicity

A novel gene involved in cytotoxicity, NKLAM [for "natural killer (NK) lytic-associated molecule"], has recently been identified in human NK cells. Its expression correlates with the cytolytic activity of both NK cells and cytotoxic T cells (CTLs); treatment of these cells with NKLAM-specific antisense oligonucleotides inhibits their cytotoxic function. NKLAM encodes a zinc finger protein that resides in NK cytolytic granules. Here, we identified a second human NKLAM transcript that differs from the original only at the 3' end, extending the open reading frame, and therefore encoding a significantly longer protein (731 residues compared with 587). The genomic structure of human NKLAM indicates that these two isoforms are products of alternative splicing. Both forms of NKLAM protein are expressed in NK cells, with the larger protein predominant. Human NKLAM cDNA was used to isolate mouse NKLAM from a C57BL/6 spleen cDNA library. There is a single NKLAM isoform in the mouse which shares over 89% nucleotide and 94% amino acid homology with the larger human form of NKLAM. The genomic organization of NKLAM is similar in both mouse and human. As with human NKLAM, mouse NKLAM mRNA is selectively expressed in CD8+ T cells NK cells, and activated peritoneal macrophages and further induced by cytokines that enhance the cytotoxic activity of these cells. These results indicate that human and mouse NKLAM are highly conserved both structurally and functionally, reinforcing the premise that this gene plays an important role in cellular cytotoxicity.