| First Author | MacMicking JD | Year | 1997 |
| Journal | Proc Natl Acad Sci U S A | Volume | 94 |
| Issue | 10 | Pages | 5243-8 |
| PubMed ID | 9144222 | Mgi Jnum | J:40374 |
| Mgi Id | MGI:87713 | Doi | 10.1073/pnas.94.10.5243 |
| Citation | MacMicking JD, et al. (1997) Identification of nitric oxide synthase as a protective locus against tuberculosis. Proc Natl Acad Sci U S A 94(10):5243-8 |
| abstractText | Mutagenesis of the host immune system has helped identify response pathways necessary to combat tuberculosis. Several such pathways may function as activators of a common protective gene: inducible nitric oxide synthase (NOS2). Here we provide direct evidence for this gene controlling primary Mycobacterium tuberculosis infection using mice homozygous for a disrupted NOS2 allele. NOS2(-/-) mice proved highly susceptible, resembling wild-type littermates immunosuppressed by high-dose glucocorticoids, and allowed Mycobacterium tuberculosis to replicate faster in the lungs than reported for other gene-deficient hosts. Susceptibility appeared to be independent of the only known naturally inherited antimicrobial locus, NRAMP1. Progression of chronic tuberculosis in wild-type mice was accelerated by specifically inhibiting NOS2 via administration of N6-(1-iminoethyl)-L-lysine. Together these findings identify NOS2 as a critical host gene for tuberculostasis. |
