ALPHA-MANNOSIDASE-II DEFICIENCY RESULTS IN DYSERYTHROPOIESIS AND UNVEILS AN ALTERNATE PATHWAY IN OLIGOSACCHARIDE BIOSYNTHESIS

Alpha-mannosidase-II (alpha M-II) catalyzes the first committed step i n the biosynthesis of complex asparagine-linked (N-linked) oligosaccha rides (N-glycans). Genetic deficiency of alpha M-II should abolish com plex N-glycan production as reportedly does inhibition of alpha M-II b y swainsonine. We find that mice lacking a functional alpha M-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 distin ct alpha-mannosidase. These studies reveal cell-type-specific variatio ns in N-linked oligosaccharide biosynthesis and an essential role for alpha M-II in the formation of erythroid complex N-glycans. alpha M-II deficiency elicits a phenotype in mice that correlates with human con genital dyserythropoietic anemia type II.