Phenotypic characterization of epiphycan-deficient and epiphycan/biglycan double-deficient mice

S. Nuka, W. Zhou, S. P. Henry, C. M. Gendron, J. B. Schultz, T. Shinomura, J. Johnson, Y. Wang, D. R. Keene, R. Ramírez-Solis, R. R. Behringer, M. F. Young, M. Höök

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Objective: To characterize the in vivo role epiphycan (Epn) has in cartilage development and/or maintenance. Methods: Epn-deficient mice were generated by disrupting the Epn gene in mouse embryonic stem cells. Epn/biglycan (Bgn) double-deficient mice were produced by crossing Epn-deficient mice with Bgn-deficient mice. Whole knee joint histological sections were stained using van Gieson or Fast green/Safranin-O to analyze collagen or proteoglycan content, respectively. Microarray analysis was performed to detect gene expression changes within knee joints. Results: Epn-deficient and Epn/Bgn double-deficient mice appeared normal at birth. No significant difference in body weight or femur length was detected in any animal at 1 month of age. However, 9-month Epn/Bgn double-deficient mice were significantly lighter and had shorter femurs than wild type mice, regardless of gender. Male Epn-deficient mice also had significantly shorter femurs than wild type mice at 9 months. Most of the deficient animals developed osteoarthritis (OA) with age; the onset of OA was observed earliest in Epn/Bgn double-deficient mice. Message RNA isolated from Epn/Bgn double-deficient knee joints displayed increased matrix protein expression compared with wild type mice, including other small leucine-rich proteoglycan (SLRP) members such as asporin, fibromodulin and lumican. Conclusion: Similar to other previously studied SLRPs, EPN plays an important role in maintaining joint integrity. However, the severity of the OA phenotype in the Epn/Bgn double-deficient mouse suggests a synergy between these two proteins. These data are the first to show a genetic interaction involving class I and class III SLRPs in vivo.

Original languageEnglish (US)
Pages (from-to)88-96
Number of pages9
JournalOsteoarthritis and Cartilage
Issue number1
StatePublished - Jan 2010


  • Cartilage
  • Microarray
  • Mouse
  • Osteoarthritis
  • Small leucine-rich proteoglycans

ASJC Scopus subject areas

  • Biomedical Engineering
  • Orthopedics and Sports Medicine
  • Rheumatology


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