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A more recent version of this article appeared on October 8, 2004
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Papers In Press, published online ahead of print July 29, 2004
J. Biol. Chem, 10.1074/jbc.M405382200
Submitted on May 14, 2004
Revised on July 29, 2004
Accepted on July 29, 2004

Heparan sulfate structure in mice with genetically modified heparan sulfate production

Johan Ledin, Will Staatz, Jin-Ping Li, Martin Götte, Scott Selleck, Lena Kjellén, and Dorothe Spillmann

Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala 75123

Corresponding Author: Dorothe.Spillmann{at}imbim.uu.se

Using a high throughput heparan sulfate (HS) isolation and characterization protocol, we have analyzed HS structure in several tissues from mice/mouse embryos deficient in HS biosynthesis enzymes (N-deacetylase/N-sulfotransferase (NDST)-1, NDST-2 and C5 epimerase respectively) and in mice lacking syndecan-1. The results have given us new information regarding HS biosynthesis with implications on the role of HS in embryonic development. Our main conclusions are: 1) The HS content, disaccharide composition, the overall degree of N- and O-sulfation as well as domain organization are characteristic for each individual mouse tissue; 2) Removal of a key biosynthesis enzyme (NDST-1 or C5 epimerase) results in similar structural alterations in all tissues analyzed; 3) Essentially no variation in HS tissue structure is detected when individuals of the same genotype are compared; 4) NDST-2, although generally expressed, does not contribute significantly to tissue specific HS-structures; 5) No change in HS structure could be detected in syndecan-1 deficient mice.


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