Gene targeting in the mouse nervous system

Our understanding of the development, connectivity and function of the nervous system has been facilitated by gene targeting technology. Here we summarize the historic background and the current state of this experimental approach with specific regard to neuroscience research. I. The Pioneering Experiments. Random mutagenesis is a very powerful method for elucidating gene function in simpler model organisms. Given the size of the genome and slow reproductive cycles, however, a more direct approach is required for mammalian models. This need was met in the early 1980's by establishing gene targeting in embryonic stem cells, later nicknamed mouse knockout. This technology was born at the confluence of two lines of experimentation: Firstly, the capacity of most mammalian somatic cells to carry out homologous recombination between endogenous loci and exogenous DNA was discovered. Secondly, pluripotent embryonic stem cell lines have been established that maintained the ability to intermingle with the early mouse embryo and contribute to the germline, thereby conferring heritability, even after extensive culturing in vitro.