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Molecular and Cellular Biology, October 2009, p. 5517-5528, Vol. 29, No. 20
0270-7306/09/$08.00+0     doi:10.1128/MCB.00430-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Dermatan Sulfate Epimerase 1-Deficient Mice Have Reduced Content and Changed Distribution of Iduronic Acids in Dermatan Sulfate and an Altered Collagen Structure in Skin{triangledown}

Marco Maccarana,1* Sebastian Kalamajski,2 Mads Kongsgaard,3 S. Peter Magnusson,3 Åke Oldberg,2 and Anders Malmström1

Department of Experimental Medical Science, Biomedical Center D12,1 B12, Lund University, SE-221 84 Lund, Sweden,2 Institute of Sports Medicine, Bispebjerg Hospital, Bispebjerg Bakke 23, DK 2400 Copenhagen NV, Denmark3

Received 2 April 2009/ Returned for modification 29 June 2009/ Accepted 25 July 2009

Dermatan sulfate epimerase 1 (DS-epi1) and DS-epi2 convert glucuronic acid to iduronic acid in chondroitin/dermatan sulfate biosynthesis. Here we report on the generation of DS-epi1-null mice and the resulting alterations in the chondroitin/dermatan polysaccharide chains. The numbers of long blocks of adjacent iduronic acids are greatly decreased in skin decorin and biglycan chondroitin/dermatan sulfate, along with a parallel decrease in iduronic-2-O-sulfated-galactosamine-4-O-sulfated structures. Both iduronic acid blocks and iduronic acids surrounded by glucuronic acids are also decreased in versican-derived chains. DS-epi1-deficient mice are smaller than their wild-type littermates but otherwise have no gross macroscopic alterations. The lack of DS-epi1 affects the chondroitin/dermatan sulfate in many proteoglycans, and the consequences for skin collagen structure were initially analyzed. We found that the skin collagen architecture was altered, and electron microscopy showed that the DS-epi1-null fibrils have a larger diameter than the wild-type fibrils. The altered chondroitin/dermatan sulfate chains carried by decorin in skin are likely to affect collagen fibril formation and reduce the tensile strength of DS-epi1-null skin.

* Corresponding author. Mailing address: Department of Experimental Medical Science, Biomedical Center D12, Lund University, SE-221 84 Lund, Sweden. Phone: 46 46222 9665. Fax: 46 46211 3417. E-mail: marco.maccarana{at}med.lu.se

{triangledown} Published ahead of print on 17 August 2009.

Molecular and Cellular Biology, October 2009, p. 5517-5528, Vol. 29, No. 20
0270-7306/09/$08.00+0     doi:10.1128/MCB.00430-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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