Transformation of Embryonic Stem Cells with the Human Type-II Collagen Gene and Its Expression in Chimeric Mice

Type-II collagen is the major extracellular component of developing cartilage, being synthesized in large amounts in the embryo. Its synthesis decreases as development progresses to very low levels in the adult. In the embryo, the correct regulation of type-II collagen is important not only for those structures that remain as cartilage, but also for the process of endochondral ossification whereby bone deposition occurs around a preformed cartilage model, and for the continuing growth of long bones. It is likely that primary defects in the type-II collagen gene will be found associated with some of the inherited growth disorders in man that affect cartilage or bone development (McKusick 1972; Cheah 1985; Stoker et al. 1985). Type-II collagen is made almost exclusively by chondrocytes which arise as condensations of mesenchymal cells in an inductive response with overlying ectoderm (Gumpel-Pinot 1981). These cells behave in a variety of ways throughout the body, and...