Models for Gain-of-Function and Loss-of-Function of MMPs: Transgenic and Gene Targeted Mice

The most powerful approach for studying gene function in an intact animal is to regulate the levels of the gene product and thereby see gains-of-function or losses-of-function. The occasional mutation in the genes for the matrix metalloproteinases or their inhibitors, or polymorphism in their promoters that alter transcriptional regulation has been identified in humans and has helped define the function of these proteins. With ever increasing sophistication in producing targeted mutations in mice, there are now available null mutation in most of the known genes for the matrix metalloproteinases and their inhibitors. A number of mouse strains with ectopic expression of normal and mutant proteins have also been made. These transgenic mice are giving us new insights into the processes of development and pathogenesis.