title: Alpha-mannosidase-II deficiency results in dyserythropoiesis and unveils an alternate pathway in oligosaccharide biosynthesis.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute and Division of Cellular and Molecular Medicine, University of California San Diego, La Jolla 92093, USA.
authors.forename: D
authors.initials: D
authors.lastname: Chui
authors.forename: M
authors.initials: M
authors.lastname: Oh-Eda
authors.forename: Y F
authors.initials: YF
authors.lastname: Liao
authors.forename: K
authors.initials: K
authors.lastname: Panneerselvam
authors.forename: A
authors.initials: A
authors.lastname: Lal
authors.forename: K W
authors.initials: KW
authors.lastname: Marek
authors.forename: H H
authors.initials: HH
authors.lastname: Freeze
authors.forename: K W
authors.initials: KW
authors.lastname: Moremen
authors.forename: M N
authors.initials: MN
authors.lastname: Fukuda
authors.forename: J D
authors.initials: JD
authors.lastname: Marth
mesh_terms: D000483:Alleles; D000742:Anemia, Dyserythropoietic, Congenital / Q000201:enzymology* / Q000235:genetics; D000818:Animals; D001216:Asparagine; D002240:Carbohydrate Sequence; D004195:Disease Models, Animal; D004910:Erythrocyte Membrane / Q000378:metabolism; D005091:Exons; D016368:Frameshift Mutation; D015723:Gene Library; D006017:Glycolipids / Q000097:blood / Q000737:chemistry / Q000302:isolation & purification; D006412:Hematopoietic Stem Cells; D006801:Humans; D008361:Mannosidases / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000096:biosynthesis* / Q000737:chemistry; D010641:Phenotype
chemical_list: D006017:Glycolipids; D009844:Oligosaccharides; D001216:Asparagine; D008361:Mannosidases; C038829:mannosyl-oligosaccharide 1,3 - 1,6-alpha-mannosidase