Comparison of acute endotoxin-induced lesions in A/J and C57BL/6J mice

Resistance to the action of endotoxin varies among inbred strains of mice, indicating that a component of this resistance has a genetic basis. Differe nt responses to endotoxin that are characteristic of individual inbred stra ins represent phenotypes that can be used to genetically map the response m odifier genes. This study compares the acute histologic lesions in 8-week-o ld mate A/J and C57BL/6J (B6) mice injected intraperitoneally with endotoxi n of E. coli O265:B6 (15 mg/kg), Animals of both strains exhibited spleniti s, splenic lymphoid hyperplasia, splenic lymphoid necrosis, and sequestrati on of neutrophils in the pulmonary alveoli. The B6 mice showed increased ma rgination of white blood cells to the pulmonary vascular endothelium relati ve to A/J mice, A large number of degenerating neutrophils was observed in the liver sinusoids of most B6 animals, while this lesion was much less sev ere in A/J mice. This difference was quantified, demonstrating a highly sig nificant difference in neutrophil infiltration in B6 mice relative to A/J m ice, Analysis of this phenotype in F-1 mice demonstrates that major genes e ncoding the trait are not X- linked, imprinted, or maternally inherited and do not show the codominant inheritance expected if Lps(d) were primarily r esponsible. The distinctive, quantitative nature of these differences provi des a useful assay for mapping genes that modify endotoxin responsiveness u sing the AXE and BXA recombinant inbred (RI) strains derived from A/J and B 6 mice.