The role of collagen II and cartilage fibril-associated molecules in skeletal development.
OBJECTIVE
The extracellular matrix (ECM) of hyaline cartilage contains an elaborated collagen fibrillar network, which is essential for the mechanical stability and the proper function of the tissue. Cartilage collagen fibrils consist of collagen II, the quantitatively minor collagens IX and XI, and several non-collagenous fibril-associated proteins. To understand the role some of these molecules in skeletal development, we have generated transgenic mouse strains harboring ablated genes for collagens II and IX, and matrilin-1.


METHODS
Mice lacking collagen II, collagen IX and matrilin-1 have been established earlier in our laboratory using standard techniques. To determine the consequences of the null mutations we used skeletal staining, histochemical and immunohistochemical assays, in situ hybridization and ultrastructural analysis.


RESULTS
Transgenic mice deficient in collagen II (Col2a1-/-) die at birth and display a severely malformed skeleton characterized by abnormal endochondral ossification and impaired intervertebral disc development. Mice lacking collagen IX (Col9a1-/-) are viable and develop an osteoarthritis-like phenotype in knee joints between 9-12 months of age. To test the possibility that the reduction in collagen II content has an influence on the onset of degenerative changes of articular cartilage, we have generated mice, which are heterozygous for the collagen II null mutation and homozygous for the collagen IX null mutation. Col2a1+/- Col9a1-/- mice show no accelerated development of osteoarthritis compared with the collagen IX knockout animals. Finally, mice lacking matrilin-1, a non-collagenous glycoprotein that binds to both collagen fibrils and aggrecan, develop normally without detectable abnormalities in their skeleton.


CONCLUSIONS
Our transgenic mouse strains carrying null mutations in genes encoding cartilage ECM proteins demonstrate that these proteins have different roles during skeletal development. Collagen II is important for cartilage formation, collagen IX for cartilage maintenance and matrilin-1 is redundant.
Aszódi
A
A
Department of Experimental Pathology, Lund University, Sweden. attila.aszodi@pat.lu.se
Hunziker
E B
EB
Olsen
B R
BR
Fässler
R
R
D000818:Animals; D002358:Cartilage, Articular / Q000254:growth & development*; D024043:Collagen Type II / Q000502:physiology*; D024081:Collagen Type IX / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000502:physiology; D024021:Fibril-Associated Collagens / Q000502:physiology*; D005552:Forelimb / Q000002:abnormalities; D006023:Glycoproteins / Q000502:physiology; D006614:Hindlimb / Q000002:abnormalities; D064235:Matrilin Proteins; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D016612:Paraffin Embedding; D010641:Phenotype; D016613:Plastic Embedding; D013131:Spine / Q000002:abnormalities
D024043:Collagen Type II; D024081:Collagen Type IX; D016326:Extracellular Matrix Proteins; D024021:Fibril-Associated Collagens; D006023:Glycoproteins; C577540:Matn1 protein, mouse; D064235:Matrilin Proteins