The proposed research project is part of a larger combination of research projects the long-term goal of which is to understand the function and assembly of collagenous proteins in specific tissues. the hypothesis is that the specific microarchitecture o the extra-cellular matrix in different tissues is determined by the tissue dependent expression of transcript and protein variants The proposed project concentrates on revealing the functional significance of type VIII collagen especially in the walls of blood vessel and the heart muscle, in which it is known to be expressed. Different mutated type VIII collagen gene constructs will be made and introduced into embryonic stem cells to be able to obtain chimeric mice. Both dominant-negative and knock-out mutants will be produced. Studies on the tissues of these mice should make it possible to see and better understand the consequences of defective type VIII collagen. This would enable the identification of disease phenotypes in humans caused by mutations in the type VIII collagen genes. Ultimately blood samples from patients with resembling phenotypes would be collected and screened for type VIII collagen gene mutations.
