The purpose of this project is to understand the molecular basis of connective tissue components as well as their gene regulation in normal development and in disease state using transgenic mice as models. Transgenic mice created by injection of DNA into mouse embryos have been exploited for the elucidation of factors which determine tissue specificity of gene expression. Phenotypic changes due to expression of foreign gene center the control of tissue specific heterologous promoters have also been studied. Creation of transgenic animals which carry mutated exogenous genes as models for human genetic diseases of cartilage and basement membrane have been exploited. Recently developed technique of targeted homologous recombination makes it possible to suppress the function of a specific function. We are establishing embryonic stem (ES) cell lines carrying a gene targeted by homologous recombination of exogenous DNA construct and introducing recipient blastogenesis in an effort to obtain chimeric mice that contain the altered genetic information in their germ line.
