title: Respiratory distress and neonatal lethality in mice lacking Golgi alpha1,2-mannosidase IB involved in N-glycan maturation.
abstract: There are three mammalian Golgi alpha1,2-mannosidases, encoded by different genes, that form Man5GlcNAc2 from Man(8-9)GlcNAc2 for the biosynthesis of hybrid and complex N-glycans. Northern blot analysis and in situ hybridization indicate that the three paralogs display distinct developmental and tissue-specific expression. The physiological role of Golgi alpha1,2-mannosidase IB was investigated by targeted gene ablation. The null mice have normal gross appearance at birth, but they display respiratory distress and die within a few hours. Histology of fetal lungs the day before birth indicate some delay in development, whereas neonatal lungs show extensive pulmonary hemorrhage in the alveolar region. No significant histopathological changes occur in other tissues. No remarkable ultrastructural differences are detected between wild type and null lungs. The membranes of a subset of bronchiolar epithelial cells are stained with lectins from Phaseolus vulgaris (leukoagglutinin and erythroagglutinin) and Datura stramonium in wild type lungs, but this staining disappears in lungs from null mice. Mass spectrometry of N-glycans from different tissues shows no significant changes in global N-glycans of null mice. Therefore, only a few glycoproteins required for normal lung function depend on alpha1,2-mannosidase IB for maturation. There are no apparent differences in the expression of several lung epithelial cell and endothelial cell markers between null and wild type mice. The alpha1,2-mannosidase IB null phenotype differs from phenotypes caused by ablation of other enzymes in N-glycan biosynthesis and from other mouse gene disruptions that affect pulmonary development and function.
authors.affiliation: McGill Cancer Centre, McGill University, Montréal, Québec, Canada.
authors.forename: Linda O
authors.initials: LO
authors.lastname: Tremblay
authors.forename: Erzsebet
authors.initials: E
authors.lastname: Nagy Kovács
authors.forename: Eugene
authors.initials: E
authors.lastname: Daniels
authors.forename: Nyet Kui
authors.initials: NK
authors.lastname: Wong
authors.forename: Mark
authors.initials: M
authors.lastname: Sutton-Smith
authors.forename: Howard R
authors.initials: HR
authors.lastname: Morris
authors.forename: Anne
authors.initials: A
authors.lastname: Dell
authors.forename: Edwige
authors.initials: E
authors.lastname: Marcinkiewicz
authors.forename: Nabil G
authors.initials: NG
authors.lastname: Seidah
authors.forename: Colin
authors.initials: C
authors.lastname: McKerlie
authors.forename: Annette
authors.initials: A
authors.lastname: Herscovics
mesh_terms: D000818:Animals; D005260:Female; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D006056:Golgi Apparatus / Q000201:enzymology / Q000235:genetics*; D037102:Lectins; D008168:Lung / Q000196:embryology / Q000378:metabolism; D008361:Mannosidases / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D011134:Polysaccharides / Q000378:metabolism; D011247:Pregnancy; D012131:Respiratory Insufficiency / Q000235:genetics*
chemical_list: D037102:Lectins; D011134:Polysaccharides; D008361:Mannosidases; C046090:mannosyl-oligosaccharide 1,2-alpha-mannosidase