Depletion of cartilage collagen fibrils in mice carrying a dominant negative Col2a1 transgene affects chondrocyte differentiation

Ottavia Barbieri, Simonetta Astigiano, Monica Morini, Sara Tavella, Anna Schito, Alessandro Corsi, Davide Di Martino, Paolo Bianco, Ranieri Cancedda, Silvio Garofalo

Research output: Contribution to journalArticle

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 languageEnglish
JournalAmerican Journal of Physiology - Cell Physiology
Volume285
Issue number6 54-6
Publication statusPublished - Dec 2003

    Fingerprint

Keywords

  • Cartilage extracellular matrix
  • Growth plate
  • Skeletal dyplasias
  • Spondyloepiphyseal dysplasia congenita

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

Cite this

Barbieri, O., Astigiano, S., Morini, M., Tavella, S., Schito, A., Corsi, A., Di Martino, D., Bianco, P., Cancedda, R., & Garofalo, S. (2003). Depletion of cartilage collagen fibrils in mice carrying a dominant negative Col2a1 transgene affects chondrocyte differentiation. American Journal of Physiology - Cell Physiology, 285(6 54-6).