Genetic engineering of neural function in transgenic rodents: towards a comprehensive strategy?

As mammalian genome projects move towards completion, the attention of mole cular neuroscientists is currently moving away from gene identification tow ards both cell-specific gene expression patterns (neuronal transcriptions) and protein expression/interactions (neuronal proteomics). In the long term , attention will increasingly be directed towards experimental intervention s which are able to question neuronal function in a sophisticated manner th at is cognisant of both transcriptomic and proteomic organization. Central to this effort will be the application of a new generation of transgenic ap proaches which are now evolving towards an appropriate level of molecular, temporal and spatial resolution. In this review, we summarize recent develo pments in transgenesis, and show how they have been applied in the principa l model species for neuroscience, namely rats and mice. Current concepts of transgene design are also considered together with an overview of new gene tically-encoded tools including both cellular indicators such as fluorescen t activity reporters, and cellular regulators such as dominant negative sig nalling factors. Application of these tools in a whole animal context can b e used to question both basic concepts of brain function, and also current concepts of underlying dysfuction in neurological diseases. (C) 2001 Elsevi er Science B.V. All rights reserved.