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Research Description:
Our research efforts are directed towards the analysis of the developmental programs mediating pattern formation, organogenesis and neurogenesis in the mouse. Towards achieving these goals, we have pioneered the technology required for generating mutations in any gene in the mouse. This technology employs the exchange of DNA sequences, by homologous recombination, between exogenous, newly added DNA sequences and the cognate chromosomal DNA sequences in embryo-derived mouse stem (ES ) cells. This process is referred to as gene-targeting. The ES cells containing the desired targeting event are then used to generate mouse germ line chimeras, capable of transmitting the mutation to their progeny. We are using this technology to determine the function of genes believed to mediate important developmental decisions in the mouse embryo. This technology is also being used to generate mouse models for human genetic diseases. Such animals allow a deeper analysis of the pathogenesis of the human disease, as well as provide appropriate subjects for testing new therapeutic protocols including somatic gene therapy. Eventually, this technology should also provide an avenue for directly correcting genetic defects in humans via somatic gene therapy. Recent research in the laboratory has focused on utilizing gene targeting to generate mutant mice to analyze the roles of the fibroblast growth factors (FGFs), the Wnt family of signaling molecules, and the Hox family of proteins in mammalian development. The laboratory has focused primarily on further understanding of the roles of these gene families in limb development and in hindbrain development.
Research Keywords:
The molecular genetic analysis of early mouse development, neural development in mammals, production of murine models of human genetic diseases, gene therapy, homologous recombination/gene targeting, programmed genomic rearrangements in the mouse, developmental and behavioral neuroscience