PMID- 10466727
OWN - NLM
STAT- MEDLINE
DCOM- 19990908
LR  - 20061115
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 400
IP  - 6746
DP  - 1999 Aug 19
TI  - Abnormal mast cells in mice deficient in a heparin-synthesizing enzyme.
PG  - 773-6
AB  - Heparin is a sulphated polysaccharide, synthesized exclusively by
      connective-tissue-type mast cells and stored in the secretory granules in complex
      with histamine and various mast-cell proteases. 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. The initial modification step, catalysed by the 
      enzyme glucosaminyl N-deacetylase/N-sulphotransferase-2, NDST-2, 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.
FAU - Forsberg, E
AU  - Forsberg E
AD  - Department of Cell and Molecular Biology, University of Uppsala, Sweden.
FAU - Pejler, G
AU  - Pejler G
FAU - Ringvall, M
AU  - Ringvall M
FAU - Lunderius, C
AU  - Lunderius C
FAU - Tomasini-Johansson, B
AU  - Tomasini-Johansson B
FAU - Kusche-Gullberg, M
AU  - Kusche-Gullberg M
FAU - Eriksson, I
AU  - Eriksson I
FAU - Ledin, J
AU  - Ledin J
FAU - Hellman, L
AU  - Hellman L
FAU - Kjellen, L
AU  - Kjellen L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Sulfates)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 9005-49-6 (Heparin)
RN  - EC 2.8.2.- (Ndst2 protein, mouse)
RN  - EC 2.8.2.- (Sulfotransferases)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - EC 3.4.21.39 (Chymases)
RN  - EC 3.5.- (Amidohydrolases)
SB  - IM
CIN - Nature. 1999 Aug 19;400(6746):714-5. PMID: 10466718
MH  - Amidohydrolases/deficiency/genetics/*metabolism
MH  - Animals
MH  - Cell Count
MH  - Cell Differentiation
MH  - Chymases
MH  - Crosses, Genetic
MH  - Female
MH  - Gene Targeting
MH  - Genotype
MH  - Heparin/*biosynthesis/metabolism
MH  - Immunoglobulin E/immunology
MH  - Male
MH  - Mast Cells/*enzymology/ultrastructure
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mutagenesis
MH  - Neutrophils/immunology
MH  - Peritoneum/pathology
MH  - Serine Endopeptidases/metabolism
MH  - Stem Cells
MH  - Sulfates/metabolism
MH  - Sulfotransferases/deficiency/genetics/*metabolism
EDAT- 1999/08/31 09:00
MHDA- 2001/03/23 10:01
CRDT- 1999/08/31 09:00
PHST- 1999/08/31 09:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/08/31 09:00 [entrez]
AID - 10.1038/23488 [doi]
PST - ppublish
SO  - Nature. 1999 Aug 19;400(6746):773-6. doi: 10.1038/23488.