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Agm1/Pgm-3-mediated sugar nucleotide synthesis is essential for hematopoiesis and development


Greig, KT; Antonchuk, J; Metcalf, D; Morgan, PO; Krebs, DL; Zhang, JG; Hacking, DF; Bode, L; Robb, L; Kranz, C; de Graaf, C; Bahlo, M; Nicola, NA; Nutt, SL; Freeze, HH; Alexander, WS; Hilton, DJ; Kile, BT
2007-08
MOLECULAR AND CELLULAR BIOLOGY
Journal Article
27
16
5849-5859
Carbohydrate modification of proteins includes N-linked and O-linked glycosylation, proteoglycan formation, glycosylphosphatidylinositol anchor synthesis, and O-GIcNAc modification. Each of these modifications requires the sugar nucleotide UDP-GlcNAc, which is produced via the hexosamine biosynthesis pathway. A key step in this pathway is the interconversion of GicNAc-6-phosphate (GlcNAc-6-P) and GlcNAc-1-P, catalyzed by phosphoglucomutase 3 (Pgm3). In this paper, we describe two hypomorphic alleles of mouse Pgm3 and show there are specific physiological consequences of a graded reduction in Pgm3 activity and global UDP-GlcNAc levels. Whereas mice lacking Pgm3 die prior to implantation, animals with less severe reductions in enzyme activity are sterile, exhibit changes in pancreatic architecture, and are anemic, leukopenic, and thrombocytopenic. These phenotypes are accompanied by specific rather than wholesale changes in protein glycosylation, suggesting that while universally required, the functions of certain proteins and, as a consequence, certain cell types are especially sensitive to reductions in Pgm3 activity.
AMER SOC MICROBIOLOGY
ANGIOTENSIN-CONVERTING ENZYME; ACETYLGLUCOSAMINE-PHOSPHATE MUTASE; PROTEIN-LOSING ENTEROPATHY; O-GLCNAC TRANSFERASE; MICE LACKING; BLOOD-PRESSURE; MALE-FERTILITY; C-MPL; GENE; MOUSE
10.1128/MCB.00802-07
Refer to copyright notice on published article.

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