Ultrastructural cartilage abnormalities in MIA/CD-RAP-deficient mice

Markus Moser, Anja Katrin Bosserhoff, Ernst B. Hunziker, Linda Sandell, Reinhard Fässler, Reinhard Buettner

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

MIA/CD-RAP is a small, soluble protein secreted from malignant melanoma cells and from chondrocytes. Recent evidence has identified MIA/CD-RAP as the prototype of a small family of extracellular proteins adopting an SH3 domain-like fold. It is thought that interaction between MIA/CD-RAP and specific epitopes in extracellular matrix proteins regulates the attachment of tumor cells and chondrocytes. In order to study the consequences of MIA/CD-RAP deficiency in vivo, we generated mice with a targeted gene disruption. The complete absence of MIA/CD-RAP mRNA and protein expression was demonstrated by reverse transcriptase, Western blot analysis, and enzyme-linked immunosorbent assay measurements of whole-embryo extracts. MIA-/- mice were viable and developed normally, and histological examination of the organs by means of light microscopy revealed no major abnormalities. In contrast, electron microscopic studies of cartilage composition revealed subtle defects in collagen fiber density, diameter, and arrangement, as well as changes in the number and morphology of chondrocytic microvilli. Taken together, our data indicate that MIA/CD-RAP is essentially required for formation of the highly ordered ultrastructural fiber architecture in cartilage and may have a role in regulating chondrocyte matrix interactions.

Original languageEnglish
Pages (from-to)1438-1445
Number of pages8
JournalMolecular and cellular biology
Volume22
Issue number5
DOIs
StatePublished - 2002

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