Roger E Ganschow

A major objective of molecular genetics research is to understand fundamental molecular mechanisms of gene regulation in mammals. Our efforts are focused on the genetic and hormonal regulation of the enzyme beta-glucuronidase (GUS) in inbred mice. Because of the ease of experimental manipulation, the inbred mouse is a very powerful model for study of gene regulation. Principles defined with this model can be directly applied to issues in human genetics. The strategy to achieve our objectives involves identification of DNA determinants of several genetic elements which specifically serve to regulate the expression of the gene (designated Gus-s) which encodes the polypeptide structure of GUS. We have cloned and characterized the genomic DNA within and surrounding Gus-s and are presently identifying the associated regulatory sequences using a variety of gene expression assays which include the transgenic mouse. At the same time we have recently identified another structural gene which is promoted and initiated from within the first intervening sequence of Gus-s and which appears to share little, if any, coding sequence with Gus-s. This novel intermingling of genes raises a number of interesting and important questions regarding mammalian gene organization, regulation, and evolution which we have begun to address. In addition, work from this laboratory has contributed significantly to the recent characterization of a mutant strain of mice which is totally deficient in GUS, exhibiting a syndrome similar to that of the human GUS deficiency, mucopolysaccharidosis type VII. This mouse provides a potentially important model system for study of gene replacement therapy. recombinant DNA; genetic engineering

Mammalian Molecular Geneticist,Gene Regulation,Nucleic acid hybridization,Lysosomes,Mammalian (non-human) Developmental Biology,Endocrine System (vertebrate)