The central goal of this proposal is to prepare transgenic mice that will be authentic animal models of human epidermolysis (EB). Two different strategies will be employed in the experiments. One will be based on the concept of "procollagen suicide" whereby appropriately mutated genes for a collagen can be designed so as to cause synthesis of shortened pro alpha chains that associate with normal pro alpha chains synthesized from the endogenous mouse gene and cause their degradation. The second strategy will be to use mutated collagen genes for homologous recombination in embryonic stem cells and with the embryonic stem cells produce transgenic mice in which the endodgenous gene for a collagen is replaced by a mutated gene. The Specific Aims of the project will be: 1. To prepare a series of constructs for the type VII gene that can be used to produce depletion of type VII collagen through procollagen suicide and a series of constructs of the gene that can be used for homologous recombination. 2. To use the gene constructs to produce transgenic mice that are authentic animal models of EB. 3. To examine in detail the pathetiology of the disease in the transgenic mice. 4. To carry out experiments with transfected cells expressing the mutated genes to see if expression of the genes can be specifically inhigited by one of several antisense strategies.
NIH ExPorter
NIH ExPorter