Transgenic mice overexpressing nNOS in the adult nervous system.

Nitric oxide (NO) has a profound role in the generation, differentiation, survival, and physiology of neurons. We have created a novel transgenic model to study the action of NO in the adult brain, in which the neuronal isoform of NO synthase (nNOS) is expressed under control of the promoter of the calcium-calmodulin multifunctional kinase IIalpha (CaMKIIalpha) gene. We show that the transgenic nNOS RNA and protein are expressed in the cortex, the hippocampus and the striatum of the transgenic mice. We also show that expression of several genes involved in the protection of neurons from oxidative stress and cell death is not affected in neurons of the transgenic mice. Furthermore, generation of new cells is depressed in the neurogenic brain areas in transgenics. In addition, we analyze gene expression in the hippocampus of the transgenic animals using microarray RNA profiling and Q-PCR. Our experiments describe specific changes in cell division and gene activity in the CaMKII-nNOS transgenic model and demonstrate its utility for studying the action of NO in the adult brain.