Perlecan maintains the integrity of cartilage and some basement membranes.
Perlecan is a heparan sulfate proteoglycan that is expressed in all basement membranes (BMs), in cartilage, and several other mesenchymal tissues during development. Perlecan binds growth factors and interacts with various extracellular matrix proteins and cell adhesion molecules. Homozygous mice with a null mutation in the perlecan gene exhibit normal formation of BMs. However, BMs deteriorate in regions with increased mechanical stress such as the contracting myocardium and the expanding brain vesicles showing that perlecan is crucial for maintaining BM integrity. As a consequence, small clefts are formed in the cardiac muscle leading to blood leakage into the pericardial cavity and an arrest of heart function. The defects in the BM separating the brain from the adjacent mesenchyme caused invasion of brain tissue into the overlaying ectoderm leading to abnormal expansion of neuroepithelium, neuronal ectopias, and exencephaly. Finally, homozygotes developed a severe defect in cartilage, a tissue that lacks BMs. The chondrodysplasia is 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 from degradation.
Costell
M
M
Department of Experimental Pathology, Lund University, S-221 85 Lund, Sweden.
Gustafsson
E
E
Aszódi
A
A
Mörgelin
M
M
Bloch
W
W
Hunziker
E
E
Addicks
K
K
Timpl
R
R
Fässler
R
R
D000818:Animals; D001485:Basement Membrane / Q000002:abnormalities / Q000254:growth & development / Q000502:physiology; D002113:Calcification, Physiologic / Q000235:genetics; D002356:Cartilage / Q000002:abnormalities / Q000254:growth & development / Q000502:physiology*; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D005097:Exostoses, Multiple Hereditary / Q000235:genetics; D018390:Gene Targeting; D005804:Genes, Lethal; D006330:Heart Defects, Congenital / Q000235:genetics; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006720:Homozygote; D051379:Mice; D020297:Mice, Congenic; D008817:Mice, Mutant Strains; D016254:Mutagenesis, Insertional; D009436:Neural Tube Defects / Q000235:genetics; D009999:Ossification, Heterotopic / Q000235:genetics; D011509:Proteoglycans / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015183:Restriction Mapping
D003094:Collagen; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D011509:Proteoglycans; C071927:perlecan