In many cases naturally occurring animal models of human inherited disorders, especially those affecting the nervous system, have not been described. In those instances where the gene defect has been identified, the introduction of mutant DNA into the germ line of mice can provide a unique opportunity to generate mice having appropriate phenotypes where disease pathogenesis and treatment can be studied. Transgenic mice are generated by both pronuclear microinjection of DNA into fertilized eggs and by introduction into blastocyst stage mouse embryos of murine embryonic stem cells that have been genetically modified by gene targeting. In addition to the generation of """"""""null allele"""""""" or """"""""knockout"""""""" mice, techniques have been developed for the introduction of subtle mutations into the germline of mice. Transgenic mice with genes under the control of cell (including glia and neurons) or tissue specific inducible/repressible promoters are also under study, particularly with respect to gene expression in the nervous system. Murine models of inherited disorders affecting the nervous system are being produced using these techniques, and the developmental and tissue specific expression of genes is characterized in these transgenic mice. Our collaborative efforts to generate transgenic mouse models of human disorders are providing valuable tools extending our understanding of disorders affecting the nervous system and for the evaluation of new treatments, including protein/enzyme replacement, cellular transplantation, and gene transfer therapies.
