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Perlecan is essential for cartilage and cephalic development.

Perlecan, a large, multi-domain, heparan sulfate proteoglycan originally identified in basement membrane, interacts with extracellular matrix proteins, growth factors and receptors, and influences cellular signalling. Perlecan is present in a variety of basement membranes and in other extracellular matrix structures. We have disrupted the gene encoding perlecan (Hspg2) in mice. Approximately 40% of Hspg2-/- mice died at embryonic day (E) 10.5 with defective cephalic development. The remaining Hspg2-/- mice died just after birth with skeletal dysplasia characterized by micromelia with broad and bowed long bones, narrow thorax and craniofacial abnormalities. Only 6% of Hspg2-/- mice developed both exencephaly and chondrodysplasia. Hspg2-/- cartilage showed severe disorganization of the columnar structures of chondrocytes and defective endochondral ossification. Hspg2-/- cartilage matrix contained reduced and disorganized collagen fibrils and glycosaminoglycans, suggesting that perlecan has an important role in matrix structure. In Hspg2-/- cartilage, proliferation of chondrocytes was reduced and the prehypertrophic zone was diminished. The abnormal phenotypes of the Hspg2-/- skeleton are similar to those of thanatophoric dysplasia (TD) type I, which is caused by activating mutations in FGFR3 (refs 7, 8, 9), and to those of Fgfr3 gain-of-function mice. Our findings suggest that these molecules affect similar signalling pathways.

Pubmed ID: 10545953


  • Arikawa-Hirasawa E
  • Watanabe H
  • Takami H
  • Hassell JR
  • Yamada Y


Nature genetics

Publication Data

November 7, 1999

Associated Grants


Mesh Terms

  • Abnormalities, Multiple
  • Animals
  • Animals, Newborn
  • Cartilage
  • Cartilage Oligomeric Matrix Protein
  • Cell Differentiation
  • Cell Division
  • Chondrocytes
  • Extracellular Matrix Proteins
  • Gene Deletion
  • Gene Expression
  • Glycoproteins
  • Growth Plate
  • Head
  • Heparan Sulfate Proteoglycans
  • Heparitin Sulfate
  • Humans
  • Matrilin Proteins
  • Mice
  • Mice, Transgenic
  • Mutagenesis, Insertional
  • Protein-Tyrosine Kinases
  • Proteoglycans
  • RNA, Messenger
  • Receptor, Fibroblast Growth Factor, Type 3
  • Receptors, Fibroblast Growth Factor
  • Thanatophoric Dysplasia