Transcriptional activation following cerebral ischemia in mice of a promoter-deleted nitric oxide synthase-2 gene

Abstract

Nitric oxide synthase (NOS)-2 is transcriptionally activated in a wide variety of injurious conditions, including cerebral ischemia, and the resulting nitric oxide is implicated both in tissue damage and recovery. Studies in vitro suggest that the proximal region of the NOS-2 promoter is obligatory for gene activation by proinflammatory cytokines. However, following cerebral ischemia in a NOS-2 gene-deficient mouse in which this region and exons 1-4 have been deleted, we find temporal and spatial expression, identical to wild-type, from a previously unidentified promoter region. The resulting protein is predicted to lack the first 113 amino acids and is NOS-2-incompetent. Fortuitously, this gene-deficient mouse presents a unique opportunity to determine more about the mechanisms of NOS-2 gene regulation in vivo.