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

Abstract

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.

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@article{Merry2001TheMP, title={The molecular phenotype of heparan sulfate in the Hs2st-/- mutant mouse.}, author={Catherine L . R . Merry and Simon L Bullock and David C. Swan and Alison C. Backen and Malcolm Lyon and Rosa S.P Beddington and Valerie A. Wilson and John Thomas Gallagher}, journal={The Journal of biological chemistry}, year={2001}, volume={276 38}, pages={35429-34} }