We have constructed a physical map of a >2-Mb region on mouse chromoso
me 6 that contains the natural killer gene complex (NKC). The map comp
rises a contig of 14 overlapping yeast artificial chromosomes onto whi
ch we positioned 25 NKC markers. NKC genetically linked genes encode >
17 proteins that directly control innate NR cell-mediated tumor lysis
and disease resistance. Herein we show that Nkrp1 genes are clustered
in a region flanked by A2m and Cd69 genes and that most Ly49 genes are
clustered in a distal region similar to 1 Mb distant. Importantly, sy
ntenic intervals of mouse chromosome 6 and human chromosome 12p that i
nclude the NKC are conserved. NKC species conservation suggests that t
he human NKC may contain orthologues for the mouse viral disease resis
tance genes, Cmv1 and Rmp1. The high-resolution NKC map will facilitat
e investigation of NKC gene regulation and identification of phenotypi
cally defined gene products that confer NR cell defense against viral
pathogens. (C) 1997 Academic Press.