[摘要]：The network organization of type IV collagen consisting of alpha 3, alpha 4, and alpha 5 chains in the glomerular basement membrane (GBM) is speculated to involve interactions of the triple helical and NC1 domain of individual alpha-chains, but in vivo evidence is lacking. To specifically address the contribution of the NC1 domain in the GBM collagen network organization, we generated a mouse with specific loss of alpha 3NC1 domain while keeping the triple helical alpha 3 chain intact by connecting it to the human alpha 5NC1 domain. The absence of alpha 3NC1 domain leads to the complete loss of the alpha 4 chain. The alpha 3 collagenous domain is incapable of incorporating the alpha 5 chain, resulting in the impaired organization of the alpha 3 alpha 4 alpha 5 chain-containing network. Although the alpha 5 chain can assemble with the alpha 1, alpha 2, and alpha 6 chains, such assembly is incapable of functionally replacing the alpha 3 alpha 4 alpha 5 protomer. This novel approach to explore the assembly type IV collagen in vivo offers novel insights in the specific role of the NC1 domain in the assembly and function of GBM during health and disease.
