Heparan sulfate structure in mice with genetically modified heparan sulfate production.
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 as follows. 1) The HS content, disaccharide composition, and 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 of the 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.
Department of Medical Biochemistry and Microbiology, University of Uppsala, SE-75123 Uppsala, Sweden.
Johan
J
Ledin
William
W
Staatz
Jin-Ping
JP
Li
Martin
M
Götte
Scott
S
Selleck
Lena
L
Kjellén
Dorothe
D
Spillmann
D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D002238:Carbohydrate Epimerases / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004187:Disaccharides / Q000737:chemistry; D005838:Genotype; D006025:Glycosaminoglycans / Q000737:chemistry / Q000378:metabolism; D006497:Heparan Sulfate / Q000096:biosynthesis / Q000737:chemistry*; D007668:Kidney / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008956:Models, Chemical; D009844:Oligosaccharides / Q000737:chemistry; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015238:Sulfotransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013552:Swine; D053668:Syndecan-1; D053667:Syndecans; D013997:Time Factors; D014018:Tissue Distribution
D000581:Amidohydrolases; D002238:Carbohydrate Epimerases; D004187:Disaccharides; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D008562:Membrane Glycoproteins; D009844:Oligosaccharides; D011509:Proteoglycans; D015238:Sulfotransferases; D053668:Syndecan-1; D053667:Syndecans; C508241:SDC1 protein, human; C508242:Sdc1 protein, mouse; C113066:NDST2 protein, human; C021350:heparitin sulfotransferase; C086519:mannuronan c-5-epimerase