Genetic engineering of neural function in transgenic rodents: towards a comprehensive strategy?
As mammalian genome projects move towards completion, the attention of molecular neuroscientists is currently moving away from gene identification towards 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 interventions which are able to question neuronal function in a sophisticated manner that is cognisant of both transcriptomic and proteomic organization. Central to this effort will be the application of a new generation of transgenic approaches which are now evolving towards an appropriate level of molecular, temporal and spatial resolution. In this review, we summarize recent developments in transgenesis, and show how they have been applied in the principal model species for neuroscience, namely rats and mice. Current concepts of transgene design are also considered together with an overview of new genetically-encoded tools including both cellular indicators such as fluorescent activity reporters, and cellular regulators such as dominant negative signalling factors. Application of these tools in a whole animal context can be used to question both basic concepts of brain function, and also current concepts of underlying dysfuction in neurological diseases.
Wells
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School of Biosciences, Cardiff University, PO Box 911, Museum Avenue, Cardiff CF10 3US, UK.
Carter
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D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics* / Q000378:metabolism; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism*; D018390:Gene Targeting / Q000379:methods; D005818:Genetic Engineering / Q000379:methods*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000502:physiology; D051381:Rats; D012377:Rodentia / Q000235:genetics* / Q000378:metabolism; D019076:Transgenes / Q000502:physiology
D009419:Nerve Tissue Proteins