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

The Lps gene (Tlr4) regulates murine responsiveness to bacterial lipopolysa ccharide (LPS). This study was designed to test the hypothesis that other g enes which control macrophage responsiveness also influence host susceptibi lity to LPS. We developed a group of recombinant mice to study the link amo ng three genes in the regulation of host sensitivity to LPS and other immun e responses; MHCII, Lps, and Nramp1. C2D (MHCII-/-, Lps(n/n), Nramp1(s/s)) mice were crossed with either C57BL10/ScN (MHCII+/+, Lps(d/d), Nramp1(s/s)) or C3H/HeJ (MHCII+/+, Lps(d/d). Nramp1(r/r)) to produce recombinants which are MHCII-/-, Lps(d/d), and Nramp1(s/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 significa ntly impact sensitivity of mice to LPS in a TNF-sensitization model. Howeve r, mice that carried the Nramp1(s/s) genotype were more sensitive to LPS-in duced sepsis.