LPS sensitivity in recombinant mice lacking functional alleles at MHCII, Lps and Nramp1 genes

Abstract

The Lps gene ( Tlr4) regulates murine responsiveness to bacterial lipopolysaccharide (LPS). This study was designed to test the hypothesis that other genes which control macrophage responsiveness also influence host susceptibility to LPS. We developed a group of recombinant mice to study the link among three genes in the regulation of host sensitivity to LPS and other immune responses; MHCII, Lps, and Nramp1. C2D (MHCII—/ —, Lpsn/n, Nramp1s/s) mice were crossed with either C57BL10/ScN (MHCII+/+, Lps d/d, Nramp1s/s) or C3H/HeJ (MHCII+/+, Lpsd/d, Nramp1r/r) to produce recombinants which are MHCII—/—, Lps d/d, and Nramp1s/s on two different mouse backgrounds. Here we describe the development and screening of these mice. In addition, we found that the absence of a functional MHCII complex did not significantly impact sensitivity of mice to LPS in a TNFsensitization model. However, mice that carried the Nramp1s/s genotype were more sensitive to LPS-induced sepsis.