Cited by 96Connective tissue disorders researchOsteoarthritis Treatment and MechanismsProteoglycans and glycosaminoglycans research

Mammalian Skeletogenesis and Extracellular Matrix. What can We Learn from Knockout Mice?

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Aszódi, Attila, F. Bateman, John, Gustafsson, Erika, Boot-Handford, Ray, Fässler, Reinhard·2000·Cell Structure and Function

Abstract

Formation of the vertebrate skeleton and the proper functions of bony and cartilaginous elements are determined by extracellular, cell surface and intracellular molecules. Genetic and biochemical analyses of human heritable skeletal disorders as well as the generation of knockout mice provide useful tools to identify the key players of mammalian skeletogenesis. This review summarises our recent work with transgenic animals carrying ablated genes for cartilage extracellular matrix proteins. Some of these mice exhibit a lethal phenotype associated with severe skeletal defects (type II collagen-null, perlecan-null), whereas others show mild (type IX collagen-null) or no skeletal abnormalities (matrilin-1-null, fibromodulin-null, tenascin-C-null). The appropriate human genetic disorders are discussed and contrasted with the knockout mice phenotypes.

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  • The organic matrix contains collagenous proteins (90%), predominantly type I collagen, and noncollagenous proteins including osteocalcin, osteonectin, osteopontin, fibronectin, bone sialoprotein II, BMPs, and growth factors.

    “The organic matrix contains collagenous proteins (90%), predominantly type I collagen, and noncollagenous proteins including osteocalcin, osteonectin, osteopontin, fibronectin and bone sialoprotein II, bone morphogenetic proteins (BMPs), and growth factors [114].”

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  1. Schenk, R.K., Felix, R., and Hofstetter, W. 1993. Morphology of connec- tive tissue: bone. In Connective Tissue and its Heritable Disorders. Mo- lecular, Genetic, and Medical Aspects (P.M. Royce, and B. Steinmann, eds.). Wiley-Liss, Inc., New York, pp. 85-101.

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Authors
Aszódi, A., F. Bateman, J., Gustafsson, E., Boot-Handford, R., & Fässler, R.
Affiliations
  • Lund University (SE)
  • Department of Paediatrics, University of Melbourne, Victoria 3052, Australia
Venue
Cell Structure and Function
Published
2000
Volume
25
Issue
2
Pages
73-84
ISSN
  • 0386-7196 (ISSN-L)
  • 1347-3700
OpenAlex
W2026056871
Cited by
96
References
67
Citations by year
2026: 1 · 2025: 3 · 2024: 1 · 2023: 1 · 2022: 5 · 2021: 6 · 2020: 3 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 3 · 2015: 4 · 2014: 4 · 2013: 3 · 2012: 1
FWCI
0.46
Type
journal article
Language
en
Open access
Locations
  • Cell Structure and Function (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
Keywords
skeletogenesis, extracellular matrix, knockout mice, type II collagen, perlecan, type IX collagen, matrilin-1, fibromodulin, tenascin-C, bone defects, transgenic mice
MeSH terms
Animals, Bone Development, Connective Tissue, Extracellular Matrix, Humans, Mice, Transgenic, Musculoskeletal Abnormalities, Mutation, Phenotype, Extracellular Matrix Proteins, Mice, Knockout, Mice

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