The molecular phenotype of heparan sulfate in the Hs2st-/- mutant mouse

C L Merry, S L Bullock, D C Swan, A C Backen, M Lyon, R S Beddington, V A Wilson, J T Gallagher

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Heparan sulfate (HS) is a co-receptor for a number of growth factors, morphogens, and adhesion proteins. HS biosynthetic modifications may determine the strength and outcome of HS-ligand interactions. We previously described the phenotype of mice with a gene-trap mutation in Hs2st, encoding the key HS 2-O-sulfotransferase enzyme in HS polymer modification. In contrast to the early developmental failure of embryos lacking HS, the onset of abnormalities in the Hs2st(-/-) mice occurs only after midgestation, the most dramatic being the complete failure of kidney development. Uronate 2-O-sulfates were not detected in the mutant HS, indicating a complete loss of function of Hs2st. However, the domain structure of the mutant HS is conserved, and compensatory increases in N- and 6-O-sulfation maintain the overall charge density. The apparent affinities of the mutant HS for hepatocyte growth factor/scatter factor and fibronectin were unchanged but were reduced for fibroblast growth factor-1 and -2. Surprisingly, the Hs2st(-/-) cells were able to mount an apparently normal signaling response to fibroblast growth factor-1 and -2 as well as to hepatocyte growth factor/scatter factor.
Original languageEnglish
Pages (from-to)35429-34
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number38
DOIs
Publication statusPublished - 2001

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