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Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice

Nature Genetics volume 20, pages 78–82 (1998)Cite this article

Abstract

The resilience and strength of bone is due to the orderly mineralization of a specialized extracellular matrix (ECM) composed of type I collagen (90%) and a host of non-collagenous proteins that are, in general, also found in other tissues. Biglycan (encoded by the gene Bgn) is an ECM proteoglycan that is enriched in bone1,2,3 and other non-skeletal connective tissues. In vitro studies indicate that Bgn may function in connective tissue metabolism by binding to collagen fibrils4 and TGF-ß (Refs 5,6), and may promote neuronal survival7. To study the role of Bgn in vivo, we generated Bgn-deficient mice. Although apparently normal at birth, these mice display a phenotype characterized by a reduced growth rate and decreased bone mass due to the absence of Bgn. To our knowledge, this is the first report in which deficiency of a non-collagenous ECM protein leads to a skeletal phenotype that is marked by low bone mass that becomes more obvious with age. These mice may serve as an animal model to study the role of ECM proteins in osteoporosis.

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Figure 1: Disruption of the mouse Bgn locus.
Figure 2: Radiological analysis of bones from Bgn+/0 and Bgn–/0 mice.
Figure 3: Histological analysis of bones from Bgn+/0 (0/+) and Bgn–/0 (0/-) mice.
Figure 4: Analysis of bone formation by in vivo labelling with fluorescent markers of mineralization.
Figure 5: Bone histomorphometry.

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Acknowledgements

We thank D. Caden and M. Mankani for X-ray analysis, D. Porter for advice with gene targeting vector and D. Eanes, N. Marino, D. Paget, J. Liang and S. Dieúdonne for help with the project.

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Authors and Affiliations

  1. Craniofacial and Skeletal Diseases Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Tianshun Xu, Larry W. Fisher, Anne-Marie Heegaard, Beatrice Sommer, Kazuhito Satomura, Pedro Dominguez, Chengyan Zhao, Pamela Gehron Robey & Marian F. Young

  2. Dipartimento di Medicina Sperimentale, University of L'Aquila, L'Aquila, 67100

    Paolo Bianco

  3. University of Rome, Rome, 00161, Italy

    Paolo Bianco

  4. Gene Targeting and Research Core Facility, National Institute of Dental Research, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Glenn Longenecker & Ashok B. Kulkarni

  5. Department of Orthopaedics, University of Michigan Medical School, Ann Arbor, 48109, Michigan, USA

    Erica Smith & Steven Goldstein

  6. Department of Pathology, University of Michigan Medical School, Ann Arbor, 48109, Michigan, USA

    Jeffrey Bonadio

  7. Mineralized Tissue Research Section, The Hospital for Special Surgery, New York, 10021, New York, USA

    Adele Boskey

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  1. Tianshun Xu
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Correspondence to Marian F. Young.

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Xu, T., Bianco, P., Fisher, L. et al. Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice. Nat Genet 20, 78–82 (1998). https://doi.org/10.1038/1746

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