Abstract
We have generated transgenic mice harboring the deletion of exon 48 in the mouse α1(II) procollagen gene (Col2a1). This was the first dominant negative mutation identified in the human α1(II) procollagen gene (COL2A1). Patients carrying a single allele with this mutation suffer from a severe skeletal disorder called spondyloepiphyseal dysplasia congenita (SED). Transgenic mice phenotype was neonatally lethal with severe respiratory failure, short bones, and cleft palate. Transgene mRNA was expressed at high levels. Growth plate cartilage of transgenic mice presented morphological abnormalities and reduced number of collagen type II fibrils. Chondrocytes carrying the mutation showed altered expression of several differentiation markers, like fibroblast growth factor receptor 3 (Fgfr3), Indian hedgehog (Ihh), runx2, cyclin-dependent kinase inhibitor P21CIP/WAF (Cdkn1a), and collagen type X (Col10a1), suggesting that a defective extracellular matrix (ECM) depleted of collagen fibrils affects chondrocytes differentiation and that this defect participates in the reduced endochondral bone growth observed in chondrodysplasias caused by mutations in COL2A1.
| Original language | English |
|---|---|
| Journal | American Journal of Physiology - Cell Physiology |
| Volume | 285 |
| Issue number | 6 54-6 |
| Publication status | Published - Dec 2003 |
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Keywords
- Cartilage extracellular matrix
- Growth plate
- Skeletal dyplasias
- Spondyloepiphyseal dysplasia congenita
ASJC Scopus subject areas
- Cell Biology
- Clinical Biochemistry
- Physiology
Cite this
Depletion of cartilage collagen fibrils in mice carrying a dominant negative Col2a1 transgene affects chondrocyte differentiation. / Barbieri, Ottavia; Astigiano, Simonetta; Morini, Monica; Tavella, Sara; Schito, Anna; Corsi, Alessandro; Di Martino, Davide; Bianco, Paolo; Cancedda, Ranieri; Garofalo, Silvio.
In: American Journal of Physiology - Cell Physiology, Vol. 285, No. 6 54-6, 12.2003.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Depletion of cartilage collagen fibrils in mice carrying a dominant negative Col2a1 transgene affects chondrocyte differentiation
AU - Barbieri, Ottavia
AU - Astigiano, Simonetta
AU - Morini, Monica
AU - Tavella, Sara
AU - Schito, Anna
AU - Corsi, Alessandro
AU - Di Martino, Davide
AU - Bianco, Paolo
AU - Cancedda, Ranieri
AU - Garofalo, Silvio
PY - 2003/12
Y1 - 2003/12
N2 - We have generated transgenic mice harboring the deletion of exon 48 in the mouse α1(II) procollagen gene (Col2a1). This was the first dominant negative mutation identified in the human α1(II) procollagen gene (COL2A1). Patients carrying a single allele with this mutation suffer from a severe skeletal disorder called spondyloepiphyseal dysplasia congenita (SED). Transgenic mice phenotype was neonatally lethal with severe respiratory failure, short bones, and cleft palate. Transgene mRNA was expressed at high levels. Growth plate cartilage of transgenic mice presented morphological abnormalities and reduced number of collagen type II fibrils. Chondrocytes carrying the mutation showed altered expression of several differentiation markers, like fibroblast growth factor receptor 3 (Fgfr3), Indian hedgehog (Ihh), runx2, cyclin-dependent kinase inhibitor P21CIP/WAF (Cdkn1a), and collagen type X (Col10a1), suggesting that a defective extracellular matrix (ECM) depleted of collagen fibrils affects chondrocytes differentiation and that this defect participates in the reduced endochondral bone growth observed in chondrodysplasias caused by mutations in COL2A1.
AB - We have generated transgenic mice harboring the deletion of exon 48 in the mouse α1(II) procollagen gene (Col2a1). This was the first dominant negative mutation identified in the human α1(II) procollagen gene (COL2A1). Patients carrying a single allele with this mutation suffer from a severe skeletal disorder called spondyloepiphyseal dysplasia congenita (SED). Transgenic mice phenotype was neonatally lethal with severe respiratory failure, short bones, and cleft palate. Transgene mRNA was expressed at high levels. Growth plate cartilage of transgenic mice presented morphological abnormalities and reduced number of collagen type II fibrils. Chondrocytes carrying the mutation showed altered expression of several differentiation markers, like fibroblast growth factor receptor 3 (Fgfr3), Indian hedgehog (Ihh), runx2, cyclin-dependent kinase inhibitor P21CIP/WAF (Cdkn1a), and collagen type X (Col10a1), suggesting that a defective extracellular matrix (ECM) depleted of collagen fibrils affects chondrocytes differentiation and that this defect participates in the reduced endochondral bone growth observed in chondrodysplasias caused by mutations in COL2A1.
KW - Cartilage extracellular matrix
KW - Growth plate
KW - Skeletal dyplasias
KW - Spondyloepiphyseal dysplasia congenita
UR - http://www.scopus.com/inward/record.url?scp=17744417389&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=17744417389&partnerID=8YFLogxK
M3 - Article
VL - 285
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6119
IS - 6 54-6
ER -