β3GNT2 (B3GNT2), A MAJOR POLYLACTOSAMINE SYNTHASE: ANALYSIS OF B3GNT2-DEFICIENT MICE
2010
Abstract The polylactosamine structure is a fundamental structure of carbohydrate chains and carries a lot of biofunctional carbohydrate epitopes. To investigate the biological function of polylactosamine chains, here we generated and analyzed knockout mice lacking the gene B3gnt2 , which encodes a major polylactosamine synthase. In β1,3- N -acetylglucosaminyltransferase (B3gnt2) B3gnt2 -deficient ( B3gnt2 −/− ) mice, the number of polylactosamine structures was markedly lower than in wild-type mice. Flow cytometry, LEL lectin-blotting, and glycan analysis by metabolic labeling demonstrated that the amount of polylactosamine chains on N -glycans was greatly reduced in the tissues of B3gnt2 −/− mice. We examined whether immunological abnormalities were present in B3gnt2 −/− mice. We screened polylactosamine-carrying molecules of wild-type mice by lectin microarray analysis and found that polylactosamine was present on CD28 and CD19, two established immune co-stimulatory molecules. Polylactosamine levels on these molecules were lower in B3gnt2 −/− mice than in wild-type mice. B3gnt2 −/− T cells were more sensitive to the induction of intracellular Ca 2+ flux on stimulation with anti-CD3e/CD28 antibodies and proliferated more strongly than wild-type T cells. B3gnt2 −/− B cells also showed hyperproliferation on BCR stimulation. These results showed that hyperactivation of lymphocytes occurred due to a lack of polylactosamine on receptor molecules in B3gnt2 −/− mice. This finding indicates that polylactosamine has an important role in immunological biofunctions. We can therefore attempt to identify the in vivo biological function of glycans using glycogene-deficient mice.
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