TY - JOUR
T1 - Ultrastructural cartilage abnormalities in MIA/CD-RAP-deficient mice
AU - Moser, Markus
AU - Bosserhoff, Anja Katrin
AU - Hunziker, Ernst B.
AU - Sandell, Linda
AU - Fässler, Reinhard
AU - Buettner, Reinhard
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0036172080&partnerID=8YFLogxK
U2 - 10.1128/MCB.22.5.1438-1445.2002
DO - 10.1128/MCB.22.5.1438-1445.2002
M3 - Article
C2 - 11839810
AN - SCOPUS:0036172080
SN - 0270-7306
VL - 22
SP - 1438
EP - 1445
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 5
ER -