J. Cell Biol.
© The Rockefeller University Press
0021-9525/97/02/729/15 $2.00
Volume 136, Number 3, February 10, 1997 729-743

Targeted Disruption of Decorin Leads to Abnormal Collagen Fibril Morphology and Skin Fragility

Keith G. Danielson,^* Helene Baribault, David F. Holmes,^§ Helen Graham,^§ Karl E. Kadler,^§ and Renato V. Iozzo^*

^* Department of Pathology, Anatomy, and Cell Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107;  The Burnham Institute, La Jolla, California 92037; ^§ Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom; and  Kimmel Cancer Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107

Decorin is a member of the expanding group of widely distributed small leucine-rich proteoglycans that are expected to play important functions in tissue assembly. We report that mice harboring a targeted disruption of the decorin gene are viable but have fragile skin with markedly reduced tensile strength. Ultrastructural analysis revealed abnormal collagen morphology in skin and tendon, with coarser and irregular fiber outlines. Quantitative scanning transmission EM of individual collagen fibrils showed abrupt increases and decreases in mass along their axes, thereby accounting for the irregular outlines and size variability observed in cross-sections. The data indicate uncontrolled lateral fusion of collagen fibrils in the decorindeficient mice and provide an explanation for the reduced tensile strength of the skin. These findings demonstrate a fundamental role for decorin in regulating collagen fiber formation in vivo.

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• Ameye, L., Young, M. F. (2002). Mice deficient in small leucine-rich proteoglycans: novel in vivo models for osteoporosis, osteoarthritis, Ehlers-Danlos syndrome, muscular dystrophy, and corneal diseases. Glycobiology 12: 107R-116R [Abstract] [Full Text]  
• Trowbridge, J. M., Gallo, R. L. (2002). Dermatan sulfate: new functions from an old glycosaminoglycan. Glycobiology 12: 117R-125R [Abstract] [Full Text]  
• Guidetti, G., Bertoni, A., Viola, M., Tira, E., Balduini, C., Torti, M. (2002). The small proteoglycan decorin supports adhesion and activation of human platelets. Blood 100: 1707-1714 [Abstract] [Full Text]  
• Xu, G., Guimond, M.-J., Chakraborty, C., Lala, P. K. (2002). Control of Proliferation, Migration, and Invasiveness of Human Extravillous Trophoblast by Decorin, a Decidual Product. Biol. Reprod. 67: 681-689 [Abstract] [Full Text]  
• Kielty, C. M., Sherratt, M. J., Shuttleworth, C. A. (2002). Elastic fibres. J. Cell Sci. 115: 2817-2828 [Abstract] [Full Text]  
• AMEYE, L., ARIA, D., JEPSEN, K., OLDBERG, A., XU, T., YOUNG, M. F. (2002). Abnormal collagen fibrils in tendons of biglycan/fibromodulin-deficient mice lead to gait impairment, ectopic ossification, and osteoarthritis. FASEB J. 16: 673-680 [Abstract] [Full Text]  
• Mavroidis, M., Capetanaki, Y. (2002). Extensive Induction of Important Mediators of Fibrosis and Dystrophic Calcification in Desmin-Deficient Cardiomyopathy. Am. J. Pathol. 160: 943-952 [Abstract] [Full Text]  
• Schaefer, L., Macakova, K., Raslik, I., Micegova, M., Grone, H.-J., Schonherr, E., Robenek, H., Echtermeyer, F. G., Grassel, S., Bruckner, P., Schaefer, R. M., Iozzo, R. V., Kresse, H. (2002). Absence of Decorin Adversely Influences Tubulointerstitial Fibrosis of the Obstructed Kidney by Enhanced Apoptosis and Increased Inflammatory Reaction. Am. J. Pathol. 160: 1181-1191 [Abstract] [Full Text]  
• Reinboth, B., Hanssen, E., Cleary, E. G., Gibson, M. A. (2002). Molecular Interactions of Biglycan and Decorin with Elastic Fiber Components. BIGLYCAN FORMS A TERNARY COMPLEX WITH TROPOELASTIN AND MICROFIBRIL-ASSOCIATED GLYCOPROTEIN 1. J. Biol. Chem. 277: 3950-3957 [Abstract] [Full Text]  
• Di Lullo, G. A., Sweeney, S. M., Korkko, J., Ala-Kokko, L., San Antonio, J. D. (2002). Mapping the Ligand-binding Sites and Disease-associated Mutations on the Most Abundant Protein in the Human, Type I Collagen. J. Biol. Chem. 277: 4223-4231 [Abstract] [Full Text]  
• Xaus, J., Comalada, M., Cardo, M., Valledor, A. F., Celada, A. (2001). Decorin inhibits macrophage colony-stimulating factor proliferation of macrophages and enhances cell survival through induction of p27Kip1 and p21Waf1. Blood 98: 2124-2133 [Abstract] [Full Text]  
• Takanosu, M., Boyd, T. C., Le Goff, M., Henry, S. P., Zhang, Y., Bishop, P. N., Mayne, R. (2001). Structure, Chromosomal Location, and Tissue-Specific Expression of the Mouse Opticin Gene. IOVS 42: 2202-2210 [Abstract] [Full Text]  
• Quantock, A. J., Meek, K. M., Chakravarti, S. (2001). An X-ray Diffraction Investigation of Corneal Structure in Lumican-Deficient Mice. IOVS 42: 1750-1756 [Abstract] [Full Text]  
• Kolb, M., Margetts, P. J., Sime, P. J., Gauldie, J. (2001). Proteoglycans decorin and biglycan differentially modulate TGF-{beta}-mediated fibrotic responses in the lung. Am. J. Physiol. Lung Cell. Mol. Physiol. 280: L1327-L1334 [Abstract] [Full Text]  
• Fischer, J. W., Kinsella, M. G., Levkau, B., Clowes, A. W., Wight, T. N. (2001). Retroviral Overexpression of Decorin Differentially Affects the Response of Arterial Smooth Muscle Cells to Growth Factors. Arterioscler. Thromb. Vasc. Bio. 21: 777-784 [Abstract] [Full Text]  
• Pluen, A., Boucher, Y., Ramanujan, S., McKee, T. D., Gohongi, T., di Tomaso, E., Brown, E. B., Izumi, Y., Campbell, R. B., Berk, D. A., Jain, R. K. (2001). Role of tumor-host interactions in interstitial diffusion of macromolecules: Cranial vs. subcutaneous tumors. Proc. Natl. Acad. Sci. USA 10.1073/pnas.081626898v1 [Abstract] [Full Text]  

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