title: Altered heparan sulfate structure in mice with deleted NDST3 gene function.
abstract: We report the generation and analysis of mutant mice bearing a targeted disruption of the heparan sulfate (HS)-modifying enzyme GlcNAc N-deacetylase/N-sulfotransferase 3 (NDST3). NDST3(-/-) mice develop normally, are fertile, and show only subtle hematological and behavioral abnormalities in agreement with only moderate HS undersulfation. Compound mutant mice made deficient in NDST2;NDST3 activities also develop normally, showing that both isoforms are not essential for development. In contrast, NDST1(-/-);NDST3(-/-) compound mutant embryos display developmental defects caused by severe HS undersulfation, demonstrating NDST3 contribution to HS synthesis in the absence of NDST1. Moreover, analysis of HS composition in dissected NDST3 mutant adult brain revealed regional changes in HS sulfation, indicating restricted NDST3 activity on nascent HS in defined wild-type tissues. Taken together, we show that NDST3 function is not essential for development or adult homeostasis despite contributing to HS synthesis in a region-specific manner and that the loss of NDST3 function is compensated for by the other NDST isoforms to a varying degree.
authors.affiliation: Department of General Zoology and Genetics, Westfälische Wilhelms-Universität Münster, Münster, Germany.
authors.forename: Srinivas R
authors.initials: SR
authors.lastname: Pallerla
authors.forename: Roger
authors.initials: R
authors.lastname: Lawrence
authors.forename: Lars
authors.initials: L
authors.lastname: Lewejohann
authors.forename: Yi
authors.initials: Y
authors.lastname: Pan
authors.forename: Tobias
authors.initials: T
authors.lastname: Fischer
authors.forename: Uwe
authors.initials: U
authors.lastname: Schlomann
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Esko
authors.forename: Kay
authors.initials: K
authors.lastname: Grobe
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D006497:Heparan Sulfate / Q000378:metabolism*; D006706:Homeostasis; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D008957:Models, Genetic; D009154:Mutation; D020033:Protein Isoforms; D011995:Recombination, Genetic; D015238:Sulfotransferases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D014018:Tissue Distribution
chemical_list: D006497:Heparan Sulfate; D020033:Protein Isoforms; D015238:Sulfotransferases; C021350:heparitin sulfotransferase