Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Perlecan is essential for cartilage and cephalic development.

Nature genetics | Nov 7, 1999

http://www.ncbi.nlm.nih.gov/pubmed/10545953

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 RIS Download

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

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

None

Mouse Genome Informatics (Data, Gene Annotation)

Comparative Toxicogenomics Database (Data, Disease Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.