The technique of gene targeting (knockout) has swept through biomedical research of the 1990s. Cytokine research has been revolutionized by knockouts and since then this technique has been widely utilized in inflammation research. This paper focuses on tuberculosis of knockout mice  among many infectious diseases. We generated knockout mice for inflammation research. After we infected the various kinds of knockout mice with Mycobacterium tuberculosis by aerosol infection,  we investigated  the roles of cytokines and transcription factors that regulate cytokines. We used knockout mice lacking IFN-g, TNF-a, IL-18, IL-1 a/b, IL-4, IL-1 type 1 receptor, NF-IL6, TLR-2, TLR-6, interferon regulatory factor-1 (IRF-1), NK-kBp 50, signal transducer and activator of trans-cription (STAT)1, STAT4 and MyD88 genes in our experimental tuberculosis research. M. tuberculosis-infected knockout mice displayed various histopathology depending on the degree of importance of the molecules in defense against tuberculosis. IFN-g, TNF-a, IRF-1, NF-IL6, NF-kB p50, STAT1 and STAT4 knockout mice succumbed to M. tuberculosis infection over time. The results indicate that these molecules play major roles for defense against tuberculosis.