THE CMV1 HOST-RESISTANCE LOCUS IS CLOSELY LINKED TO THE LY49 MULTIGENE FAMILY WITHIN THE NATURAL-KILLER-CELL GENE-COMPLEX ON MOUSE CHROMOSOME-6

Natural killer (NK) cells play important roles in controlling tumor ce lls and against a range of infectious organisms. Recent studies of mou se NK cell surface receptors, which may be involved in the specificity of NK cells, have shown that many of these molecules are encoded by t he Ly49 and Ly55 (Nkrp1) multigene families that map to distal mouse c hromosome 6. Also mapping to this NH cell gene complex (NKC) is the re sistance locus, Cmv1, which is involved in genetically determined resi stance to murine cytomegalovirus (MCMV). The aim of this study was to localize Cmv1 more precisely in relation to other NHC loci by generati ng a high-resolution genetic map of the region. We have analyzed 1250 backcross mice comprising panels of 700 (BALB/c x C57BL/6J)F-1 x BALB/ c and 550 (A/J x C57BL/6J)F-1 x A/J progeny. A total of 25 polymorphic genes or microsatellite markers were analyzed over a region of 10 map units from D6Mit134 to D6Mit59. The Cmv1 phenotypes of mice recombina nt in this interval were tested by infection with MCMV. The results ob tained indicate that the functionally important NKC region is a tightl y linked cluster of loci spanning at least 0.4 map units. Furthermore, Cmv1 maps distal to, but very closely linked to, the Ly49 multigene f amily (<0.2 map units), suggesting that MCMV resistance may be conferr ed by MHC class I-specific NH cell receptors. (C) 1997 Academic Press.