Our research efforts are directed towards the analysis of the developmental programs in which winged helix genes contribute to correct pattern formation and organogenesis. Towards achieving these goals, we use a technology that specifically mutates any gene you choose 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, thereby transferring the alteration to subsequent mouse generations.
We are now using this technology to analyze the function of winged helix genes believed to mediate important developmental decisions in the mouse. A similar approach is also being employed to study problems of more immediate relevance to human medicine. In particular, "gene-targeting" is being used to generate mouse models for human genetic diseases. Such animals will permit a deeper analysis of the pathogenesis of the genetic disease as well as provide appropriate subjects for testing new therapeutic protocols including somatic gene therapy. Eventually gene targeting should also become directly applicable toward correcting genetic defects in humans by somatic gene therapy.