Analysis of genetic factors associated with nitric oxide production in mice.

Different mouse strains possessing the Nramp1r allele, which were theoretically expected to have relatively high nitric oxide (NO) production after cytokine stimulation, were used to analyze the genetic factors associated with NO production. After gamma interferon and lipopolysaccharide stimulation, the strains NZB/N, DBA/2N, AKR/N, and A/J showed significantly low NO production; NJL, 129/J, MOG, SJL/J, CBA/N, and NOD/Shi had moderate amounts; and C3H/He and SPR had the highest levels as compared to the other mice. The F1 progeny of A/J x C3H/He and AKR/N x C3H/He showed significantly higher NO production, whereas the F1 progeny of DBA/2N x C3H/He produced a relatively low amount. Furthermore, the backcross progeny from their F1 showed variations in NO production, and therefore it was speculated that the regulation of NO production is polygenic. Genetic typing experiments related to the NO production in the backcross progeny demonstrated significant deviations to some genetic microsatellite markers. Sequencing of the iNOS promoter regions of the Nramp1r strains to examine the relationship with NO production revealed that MOG and SPR strains had substitutions within the NF-kappaB and the gamma-IRE transcription binding factor, respectively.