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

We have cloned and characterized the rat inducible nitric oxide synthase (i NOS) gene. It spans approx. 36 kb and is divided into 27 exons and 36 intro ns. 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 KB (NF kappa B)- dependent induction, but also many which may have a role in its NF kappa B- independent induction pathway. These include cyclic adenosine 3', 5'-monoph osphate (cAMP) response elements (CRE), hypoxia responsive element (HRE) an d 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 oxid e (NO) in general, the cloned rat iNOS gene will further reveal the mechani sms of iNOS inducibility in different cell types during development and dis ease, including brain diseases, and to promote studies of pharmacological i ntervention in cases where extensive NO production plays a critical role. ( C) 1999 Elsevier Science B.V. All rights reserved.