Mapping Lipopolysaccharide Response Loci in Mice Using Recombinant Inbred and Congenic Strains

Lipopolysaccharide (LPS) induces proliferation of splenic B-cells, and this response was found to be significantly lower in A/J than in C57BL/6J (B6) mice. Several strains and substrains mirrored the high and low responses of B6 and A/J. Assessment of 26 AXB/BXA recombinant inbred (RI) mouse strains identified 23 strains with a low (A/J-like), high (B6-like), or intermediate response. The three remaining RI strains exhibited a novel hyperresponsive phenotype significantly different from that of either founder strain. RI analysis identified four suggestive loci contributing to the LPS response, two of which were confirmed by analysis of congenic strains containing the donor genomic segment from a high- or low-responder strain on the opposite background. The combination of A/J and B6 alleles fixed to homozygosity at the four suggestive loci would occur in only 1 of 256 intercross progeny, but occurred several times among the RI strains.