Targeted gene disruption: applications in neurobiology.
In classical gene inactivation approaches by homologous recombination in embryonic stem cells, the resulting knockout mice are genotypically homogeneous. The inactivation of a gene in the complete organism may sometimes lead to early embryonic lethality. The observation that bacterial recombinases can drive site-specific recombination in mammalian cells has allowed for spatiotemporally controlled genetic modifications. Thus, conditional gene inactivation can be achieved in a specific subset of cells, leaving the rest of the organism genotypically unchanged. Another application of bacterial recombinases is the generation of exon-specific knockout mice, allowing for the analysis of the role of tissue-specific splice variants. A combination of the above-mentioned bacterial recombinase technique with inducible promoter systems permits the investigator to choose precisely the onset of recombination. An extension of the above-mentioned techniques is the combination of the bacterial recombinase technique with adenovirus-based technology, which would open vast possibilities of tissue-specific genetic modifications in a controlled time frame.
van der Neut
R
R
Division of Cell Biology, Netherlands Cancer Institute, Amsterdam. rneut@nki.nl
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D005091:Exons / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D017930:Genes, Reporter; D005822:Genetic Vectors; D006801:Humans; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009446:Neurobiology / Q000379:methods*; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics; D011995:Recombination, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D013234:Stem Cells / Q000378:metabolism; D014764:Viral Proteins
D001426:Bacterial Proteins; D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases