Small Leucine Rich Proteoglycans (SLRPs) constitute a family of secreted proteoglycans with structurally related core proteins. During the first funding period of this program project, we have isolated and characterized a new mammalian member of this family; Epiphycan. We show that this proteoglycan is selectively expressed in developing epiphyseal cartilage in a temporarily regulated manner. Furthermore, we have obtained through gene targeting, an epiphycan deficient mouse. Initial analyses suggest that at least some epi-/- mice are viable and appear to develop normally. Together with recently published studies of mice deficient in other SLRPs, these results suggest a redundancy of functions Among different SLRPs. This conclusion is the bases for our proposed future functions among different SLRPs. This conclusion is the bases for our proposed future studies. We have recently found a novel Zn2+ binding motif in the N-terminal domain of decorin, which in the presence of the metal ion, is capable of binding fibronectin, fibrinogen and collagen. Other SLRPs contain similar N-terminal sequences. The structure and interactions of these domains will now be analyzed. In addition to characterizing mice deficient in epiphycan or osteoglycin, we plan to generate and characterize mice deficient in multiple SLRPs. The possibility of over-expressing a segment of decorin in bone and cartilage which may interfere with matrix deposition of SLRPs, will also be explored.
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