Molecular cloning and characterization of the rat inducible nitric oxide synthase (iNOS) gene

We have cloned and characterized the rat inducible nitric oxide synthase (iNOS) gene. It spans approx. 36kb and is divided into 27 exons and 26 introns. The distribution and length of exons are similar to those in the human iNOS gene. In the 5' flanking regulatory region of the rat iNOS gene, there are a number of putative transcription factor binding sites (>20), many of them probably indispensable for the gene's nuclear factor kappaB (NFkappaB)-dependent induction, but also many which may have a role in its NFkappaB-independent induction pathway. These include cyclic adenosine 3', 5'-monophosphate (cAMP) response elements (CRE), hypoxia responsive element (HRE) and GATA-core elements. Rat models are powerful tools in studies of neurological diseases. Because iNOS is most likely responsible for the harmful consequences of nitric oxide (NO) in general, the cloned rat iNOS gene will further reveal the mechanisms of iNOS inducibility in different cell types during development and disease, including brain diseases, and to promote studies of pharmacological intervention in cases where extensive NO production plays a critical role.