Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 283, Issue 24, Pages 16885-16894Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M709774200
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Funding
- NEI NIH HHS [R01 EY018868] Funding Source: Medline
- NHLBI NIH HHS [HL57345] Funding Source: Medline
- NIGMS NIH HHS [GM33063] Funding Source: Medline
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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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