| First Author | Merry CL | Year | 2001 |
| Journal | J Biol Chem | Volume | 276 |
| Issue | 38 | Pages | 35429-34 |
| PubMed ID | 11457822 | Mgi Jnum | J:71568 |
| Mgi Id | MGI:2150438 | Doi | 10.1074/jbc.M100379200 |
| Citation | Merry CL, et al. (2001) The molecular phenotype of heparan sulfate in the Hs2st-/- mutant mouse. J Biol Chem 276(38):35429-34 |
| abstractText | 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. |
