Creation of gene targeted mutations and introduction of dominant mutations in transgenic mice have proved to be useful for understanding functions of proteins in development and as animal models for therapeutic applications for various diseases. The purpose of this project is to create transgenic mice for studying the molecular basis of genetic and acquired diseases associated with connective tissues as well as development. Genes for basement membrane and cartilage components have been cloned and the exon-intron structure of these genes have been characterized. Creation of transgenic mice with mutated exogenous genes for collagen IV and laminin chains have been exploited. Constructs for expression of foreign genes in cartilage in transgenic mice under the control of the promoter and enhancer of collagen II gene have been prepared to create animal models for human diseases such as arthritis and diabetes. Constructs containing reporter genes under the direction of promoters of the genes for collagen II and IV have been prepared and injected into mouse oocytes to identify sequences necessary for tissue specific expression. The creation of mutations in the endogenous genes for basement membrane and cartilage proteins has been attempted by homologous recombination. By using gene targeting in embryonic stem cells, mutations of specific sites within the genes can be introduced in the mouse germ line to assess the role of these genes in the whole animals.