Nitric oxide synthase, inducible is an enzyme which is encoded by the NOS2gene in humans and mice.[5]
Genetics
Three related pseudogenes are located within the Smith-Magenis syndrome region on chromosome 17. Alternative splicing of this gene results in two transcript variants encoding different isoforms.[6]
Nitric oxide is a reactive free radical mediating in neurotransmission, antimicrobial and antitumoral activities.[citation needed]
In mice, the function of Nos2 in immunity against a number of viruses, bacteria, fungi, and parasites has been well characterized, whereas in humans the role of NOS2 has remained elusive and controversial.[7] Nos2 is important for protective immunity against CMV.[8]
Autosomal recessive NOS2 deficiency has been described in mice. They lack the gene encoding nitric oxide synthase 2 (Nos2) and are susceptible to murine CMV infection.[11]
In February 2020, the same autosomal recessive, complete NOS2 deficiency was described in a human. A 51-year-old previously healthy person died after 29 months of progressive CMV infection due to respiratory failure secondary to CMV pneumonitis, CMV encephalitis, and hemophagocytic lymphohistiocytosis. Whole-exome sequencing on genomic DNA from his blood showed he had homozygous variants in five genes. The only loss-of-function variant was a homozygous frameshift mutation in nitric oxide synthase 2. This condition is extremely rare, occurring in fewer than 1 per million persons.[8]
^Kuncewicz T, Balakrishnan P, Snuggs MB, Kone BC (August 2001). "Specific association of nitric oxide synthase-2 with Rac isoforms in activated murine macrophages". American Journal of Physiology. Renal Physiology. 281 (2): F326 –F336. doi:10.1152/ajprenal.2001.281.2.F326. PMID11457725. S2CID15719851.