3 MEMBERS OF THE NITRIC-OXIDE SYNTHASE-II GENE FAMILY (NOS2A, NOS2B, AND NOS2C) COLOCALIZE TO HUMAN-CHROMOSOME-17

Nitric oxide synthases (NOSs) are a family of enzymes responsible for the synthesis of nitric oxide from L-arginine and molecular oxygen. Th ree human NOS enzymes (I, II, and III) with differing cellular distrib ution and regulatory mechanisms have been identified. To determine whe ther additional NOSs are encoded in the human genome, a bovine NOS II- related cDNA was used to screen two human genomic Libraries. Clones co ntaining three independent genes were isolated. One clone encoded the previously identified NOS II gene (NOS2A). The two other genes specifi ed amino acids homologous, but not identical, to human NOS II (NOS2B a nd NOS2C). Southern blot hybridization demonstrated that all three gen es are present in the human genome. DNA from human-mouse somatic cell hybrids were used to determine the chromosomal location of the NOS II- related genes. Ah three NOS II-related genes colocalized to human chro mosome 17 between bands p13.1 and q25. These observations suggest that there is more than one NOS II-related gene in the human genome, This finding may have important implications for the design of NOS isoform- specific inhibitors. (C) 1995 Academic Press, Inc.