論文

査読有り
2009年5月

Learning/Memory Impairment and Reduced Expression of the HNK-1 Carbohydrate in beta 4-Galactosyltransferase-II-deficient Mice

JOURNAL OF BIOLOGICAL CHEMISTRY
  • Toru Yoshihara
  • ,
  • Kazushi Sugihara
  • ,
  • Yasuhiko Kizuka
  • ,
  • Shogo Oka
  • ,
  • Masahide Asano

284
18
開始ページ
12550
終了ページ
12561
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1074/jbc.M809188200
出版者・発行元
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.

Web of Science ® 被引用回数 : 37

リンク情報
DOI
https://doi.org/10.1074/jbc.M809188200
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/19265195
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000265494600084&DestApp=WOS_CPL
ID情報
  • DOI : 10.1074/jbc.M809188200
  • ISSN : 0021-9258
  • PubMed ID : 19265195
  • Web of Science ID : WOS:000265494600084

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