Genetic rescue of chondrodysplasia and the perinatal lethal effect of cartilage link protein deficiency

Mátyás Czipri, Jeffrey M. Otto, Gabriella Cs-Szabó, Rajesh V. Kamath, Csaba Vermes, Gábor Firneisz, Kevin J. Kolman, Hideto Watanabe, Yefu Li, Peter J. Roughley, Yoshihiko Yamada, Björn R. Olsen, Tibor T. Glant

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The targeted disruption of cartilage link protein gene (Crtl1) in homozygous mice resulted in a severe chondrodysplasia and perinatal lethality. This raised the question of whether the abnormalities seen in Crtl1 null mice are all caused by the absence of link protein in cartilage or whether the deficiency of the protein in other tissues and organs contributed to the phenotype. To address this question we have generated transgenic mice overexpressing cartilage link protein under the control of a cartilage-specific promoter, and then these transgenic mice were used for a genetic rescue of abnormalities in Crtl1 null mice. While the overexpression of cartilage link protein resulted in no abnormal phenotype, the cartilage-specific transgene expression of link protein could completely prevent the perinatal mortality of link protein-deficient mice and, depending on the level of the link protein expression, rescue skeletal abnormalities. Although link protein was originally isolated from cartilage, we found and determined Crtl1 transcripts and corresponding proteins in every organ tested from mouse embryos to aging animals. We also identified three additional members of the link protein family, all co-localized with hyaluronic acid-binding proteoglycans in the mouse genome. The ubiquitous presence of link protein suggests a general and systemic function of link protein in the organization of extracellular matrix in a number of tissues, possibly interacting with other proteoglycans, such as versican, brevican, and neurocan.

Original languageEnglish
Pages (from-to)39214-39223
Number of pages10
JournalJournal of Biological Chemistry
Volume278
Issue number40
DOIs
Publication statusPublished - Oct 3 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Czipri, M., Otto, J. M., Cs-Szabó, G., Kamath, R. V., Vermes, C., Firneisz, G., Kolman, K. J., Watanabe, H., Li, Y., Roughley, P. J., Yamada, Y., Olsen, B. R., & Glant, T. T. (2003). Genetic rescue of chondrodysplasia and the perinatal lethal effect of cartilage link protein deficiency. Journal of Biological Chemistry, 278(40), 39214-39223. https://doi.org/10.1074/jbc.M303329200