The inducible form of nitric oxide synthase (iNOS or Nos2) plays a key role in the host defense of mammals to infectious agents and tumors. Nos2 deficient mice fail to restrain the replication of Listeria monocytogenes, Mycobacterium tuberculosis, Ectromelia virus, Coxsackie virus, and Leishmania major. Macrophages from these mice show impaired suppression of tumor cells in vitro
. The mice also show some protection from endotoxic shock, but many parameters of this disease process are unaffected, suggesting a critical role for other inflammatory mediators.
Genetic Background: C57BL/6 Background
This knockout line was produced as a joint collaboration between Drs. Carl Nathan and John MacMicking at Cornell University Medical College and Dr. John Mudgett at Merck Research Laboratories. The line was generated by deleting the first 4 exons and part of the promoter region of the Nos2 gene through gene targeting in 129S7-derived AB2.1 ES cells.
MacMicking JD, Nathan C, Hom G, Chartrain N, Fletcher DS, Trumbauer M, Stevens K, Xie QW, Sokol K, Hutchinson N, et al; Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase; Cell 1995 May 19;81(4):641-50