- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
The glycosylation of glycoproteins and glycolipids is important for central nervous system development and function. Although the roles of several carbohydrate epitopes in the central nervous system, including polysialic acid, the human natural killer-1 (HNK-1) carbohydrate, alpha 2,3-sialic acid, and oligomannosides, have been investigated, those of the glycan backbone structures, such as Gal beta 1-4GlcNAc and Gal beta 1-3GlcNAc, are not fully examined. Here we report the generation of mice deficient in beta 4-galactosyltransferase-II (beta 4GalT-II). This galactosyltransferase transfers Gal from UDP-Gal to a nonreducing terminal GlcNAc to synthesize the Gal beta 1-4GlcNAc structure, and it is strongly expressed in the central nervous system. In behavioral tests, the beta 4GalT-II(-/-) mice showed normal spontaneous activity in a novel environment, but impaired spatial learning/memory and motor coordination/learning. Immunohistochemistry showed that the amount of HNK-1 carbohydrate was markedly decreased in the brain of beta 4GalT-II(-/-) mice, whereas the expression of polysialic acid was not affected. Furthermore, mice deficient in glucuronyltransferase (GlcAT-P), which is responsible for the biosynthesis of the HNK-1 carbohydrate, also showed impaired spatial learning/memory as described in our previous report, although their motor coordination/learning was normal as shown in this study. Histological examination showed abnormal alignment and reduced number of Purkinje cells in the cerebellum of beta 4GalT-II(-/-) mice. These results suggest that the Gal beta 1-4GlcNAc structure in the HNK-1 carbohydrate is mainly synthesized by beta 4GalT-II and that the glycans synthesized by beta 4GalT-II have essential roles in higher brain functions, including some that are HNK-1-dependent and some that are not.
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- DOI : 10.1074/jbc.M809188200
- ISSN : 0021-9258
- PubMed ID : 19265195
- Web of Science ID : WOS:000265494600084