Alpha-mannosidase-II deficiency results in dyserythropoiesis and unveils an alternate pathway in oligosaccharide biosynthesis

Cell. 1997 Jul 11;90(1):157-67. doi: 10.1016/s0092-8674(00)80322-0.


Alpha-mannosidase-II (alphaM-II) catalyzes the first committed step in the biosynthesis of complex asparagine-linked (N-linked) oligosaccharides (N-glycans). Genetic deficiency of alphaM-II should abolish complex N-glycan production as reportedly does inhibition of alphaM-II by swainsonine. We find that mice lacking a functional alphaM-II gene develop a dyserythropoietic anemia concurrent with loss of erythrocyte complex N-glycans. Unexpectedly, nonerythroid cell types continued to produce complex N-glycans by an alternate pathway comprising a distinct alpha-mannosidase. These studies reveal cell-type-specific variations in N-linked oligosaccharide biosynthesis and an essential role for alphaM-II in the formation of erythroid complex N-glycans. alphaM-II deficiency elicits a phenotype in mice that correlates with human congenital dyserythropoietic anemia type II.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Anemia, Dyserythropoietic, Congenital / enzymology*
  • Anemia, Dyserythropoietic, Congenital / genetics
  • Animals
  • Asparagine
  • Carbohydrate Sequence
  • Disease Models, Animal
  • Erythrocyte Membrane / metabolism
  • Exons
  • Frameshift Mutation
  • Gene Library
  • Glycolipids / blood
  • Glycolipids / chemistry
  • Glycolipids / isolation & purification
  • Hematopoietic Stem Cells
  • Humans
  • Mannosidases / deficiency*
  • Mannosidases / genetics
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Oligosaccharides / biosynthesis*
  • Oligosaccharides / chemistry
  • Phenotype


  • Glycolipids
  • Oligosaccharides
  • Asparagine
  • Mannosidases
  • mannosyl-oligosaccharide 1,3 - 1,6-alpha-mannosidase