ABSTRACT
This chapter reviews the status of the technology for alteration of genes in the brain of the mouse. It focuses on the background and basic principles of transgenic mouse design and the interpretation of neurobiological and behavioral data. Transgenesis involves the introduction of a novel piece of DNA into the germ line cells of an animal. The basic methodology for the generation of a knockout involves the alteration of the locus of interest in embryonic stem (ES) cells by homologous recombination. The conditional knockout approach allows the gene of interest to be deleted specifically in the desired cell types. In general, the approaches that have attempted to obtain inducible gene knockouts in the nervous system have employed techniques that make the activity of the CRE recombinase inducible. Gene targeting transfections will generate an ES cell line carrying the mutant exon along with the neomycin-resistance gene.
