Perlecan maintains the integrity of cartilage and some basement membranes

Perlecan is a heparan sulfate proteoglycan that is expressed in all basemen t membranes (BMs). in cartilage, and several other mesenchymal tissues duri ng development. Perlecan binds growth factors and interacts with Various ex tracellular matrix proteins and cell adhesion molecules. Homozygous mice wi th a null mutation in the perlecan gene exhibit normal formation of BMs. Ho wever, BMs deteriorate in regions with increased mechanical stress such as the contracting myocardium and the expanding brain vesicles showing that pe rlecan is crucial for maintaining BM integrity. As a consequence, small cle fts are formed in the cardiac muscle leading to blood leakage into the peri cardial cavity and an arrest of heart function, The defects in the BM separ ating the brain from the adjacent mesenchyme caused invasion of brain tissu e into the overlaying ectoderm leading to abnormal expansion of neuroepithe lium, neuronal ectopias, and exencephaly. Finally, homozygotes developed a severe defect in cartilage, a tissue that lacks BMs. The chondrodysplasia i s characterized by a reduction of the fibrillar collagen network, shortened collagen fibers, and elevated expression of cartilage extracellular matrix genes, suggesting that perlecan protects cartilage extracellular matrix fr om degradation.