| First Author | Forsberg E | Year | 1999 |
| Journal | Nature | Volume | 400 |
| Issue | 6746 | Pages | 773-6 |
| PubMed ID | 10466727 | Mgi Jnum | J:57121 |
| Mgi Id | MGI:1343737 | Doi | 10.1038/23488 |
| Citation | Forsberg E, et al. (1999) Abnormal mast cells in mice deficient in a heparin-synthesizing enzyme [see comments]. Nature 400(6746):773-6 |
| abstractText | Heparin is a sulphated polysaccharide, synthesized exclusively by connective-tissue-type mast cells(1) and stored in the secretory granules in complex with histamine and various mast-cell proteases(2). Although heparin has long been used as an antithrombotic drug, endogenous heparin is not present in the blood, so it cannot have a physiological role in regulating blood coagulation. The biosynthesis of heparin involves a series of enzymatic reactions, including sulphation at various positions(1,3). The initial modification step, catalysed by the enzyme glucosaminyl N-deacetylase/N-sulphotransferase-2, NDST-2 (refs 4-7), is essential for the subsequent reactions. Here we report that mice carrying a targeted disruption of the gene encoding NDST-2 are unable to synthesize sulphated heparin. These NDST-2-deficient mice are viable and fertile but have fewer connective-tissue-type mast cells; these cells have an altered morphology and contain severely reduced amounts of histamine and mast-cell proteases. Our results indicate that one site of physiological action for heparin could be inside connective-tissue-type mast cells, where its absence results in severe defects in the secretory granules. |
