EVOLVING CONCEPTS IN MOLECULAR PATHOLOGY

During the last decade, an understanding of the causes of many human d iseases has progressed rapidly, in large measure because of the develo pment of technologies that allow us to identify the genes that are inv olved. Identification of a gene that is suspected to play an important role in a particular disease opens up a whole new dimension of resear ch to understand the molecular events that underlie the cause of that disorder. A crucial step in this process is often the development of a n animal model of the disease. Again, the last decade has seen rapid a dvances in our ability to create such models, particularly in mice. Te chnologies that allow for the addition, alteration, of elimination of individual genes from the genome to create a transgenic mouse are now routine. The advantages of having a transgenic mouse model of a human disease are many. These animals often provide the first unequivocal pr oof that a particular gene is responsible for causing the pathological changes that occur with disease. They also can provide a system to ca refully dissect the successive events that lead to the disease state, and can provide a custom-designed whole animal system to test potentia l therapies to treat and eventually cure the disease. Most important, new concepts relating to gene expression and gene function in disease often emerge from such transgenic studies. This review will illustrate several examples in which transgenic animals have contributed signifi cantly to the evolution of concepts of the underlying mechanisms of hu man disease.