Natural resistance to infection with intracellular parasites is contro
lled by a dominant gene on mouse chromosome 1, called Bcg, Lsh, or Ity
. Bcg affects the capacity of macrophages to destroy ingested intracel
lular parasites early during infection. We have assembled a 400 kb bac
teriophage and cosmid contig within the genomic interval containing Bc
g. A search for transcription units by exon amplification identified s
ix novel genes in this contig. RNA expression studies showed that one
of them, designated Nramp, was expressed exclusively in macrophage pop
ulations from reticuloendothelial organs and in the macrophage line J7
74A. Nramp encodes an integral membrane protein that has structural ho
mology with known prokaryotic and eukaryotic transport systems, sugges
ting a macrophage-specific membrane transport function. Susceptibility
to infection (Bcg(s)) in 13 Bcg(r) and Bcg(s) strains tested is assoc
iated with a nonconservative Gly-105 to Asp-105 substitution within pr
edicted transmembrane domain 2 of Nramp.