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Publication : Altered heparan sulfate structure in mice with deleted NDST3 gene function.

First Author  Pallerla SR Year  2008
Journal  J Biol Chem Volume  283
Issue  24 Pages  16885-94
PubMed ID  18385133 Mgi Jnum  J:138557
Mgi Id  MGI:3805404 Doi  10.1074/jbc.M709774200
Citation  Pallerla SR, et al. (2008) Altered heparan sulfate structure in mice with deleted NDST3 gene function. J Biol Chem 283(24):16885-94
abstractText  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.
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