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タイトル: | Lactosylceramide synthases encoded by B4galt5 and 6 genes are pivotal for neuronal generation and myelin formation in mice |
著者: | Yoshihara, Toru Satake, Hiroyuki Nishie, Toshikazu Okino, Nozomu Hatta, Toshihisa Otani, Hiroki Naruse, Chie Suzuki, Hiroshi Sugihara, Kazushi Kamimura, Eikichi Tokuda, Noriyo Furukawa, Keiko Fururkawa, Koichi Ito, Makoto Asano, Masahide |
著者名の別形: | 吉原, 亨 佐武, 寛之 西江, 敏和 沖野, 望 八田, 稔久 大谷, 浩 成瀬, 智恵 鈴木, 紘史 杉原, 一司 神村, 栄吉 徳田, 典代 古川, 圭子 古川, 鋼一 伊東, 信 浅野, 雅秀 |
発行日: | 16-Aug-2018 |
出版者: | Public Library of Science (PLoS) |
誌名: | PLOS Genetics |
巻: | 14 |
号: | 8 |
論文番号: | e1007545 |
抄録: | It is uncertain which β4-galactosyltransferase (β4GalT; gene name, B4galt), β4GalT-5 and/or β4GalT-6, is responsible for the production of lactosylceramide (LacCer) synthase, which functions in the initial step of ganglioside biosynthesis. Here, we generated conditional B4galt5 knockout (B4galt5 cKO) mice, using Nestin-Cre mice, and crossed these with B4galt6 KO mice to generate B4galt5 and 6 double KO (DKO) mice in the central nervous system (CNS). LacCer synthase activity and major brain gangliosides were completely absent in brain homogenates from the DKO mice, although LacCer synthase activity was about half its normal level in B4galt5 cKO mice and B4galt6 KO mice. The DKO mice were born normally but they showed growth retardation and motor deficits at 2 weeks and died by 4 weeks of age. Histological analyses showed that myelin-associated proteins were rarely found localized in axons in the cerebral cortex, and axonal and myelin formation were remarkably impaired in the spinal cords of the DKO mice. Neuronal cells, differentiated from neurospheres that were prepared from the DKO mice, showed impairments in neurite outgrowth and branch formation, which can be explained by the fact that neurospheres from DKO mice could weakly interact with laminin due to lack of gangliosides, such as GM1a. Furthermore, the neurons were immature and perineuronal nets (PNNs) were poorly formed in DKO cerebral cortices. Our results indicate that LacCer synthase is encoded by B4galt5 and 6 genes in the CNS, and that gangliosides are indispensable for neuronal maturation, PNN formation, and axonal and myelin formation. |
記述: | 糖脂質ガングリオシドが脳の形成に必須であることを解明 --神経系の構築異常のモデルを提示--. 京都大学プレスリリース. 2018-08-28. |
著作権等: | © 2018 Yoshihara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
URI: | http://hdl.handle.net/2433/234098 |
DOI(出版社版): | 10.1371/journal.pgen.1007545 |
PubMed ID: | 30114188 |
関連リンク: | https://www.kyoto-u.ac.jp/ja/research-news/2018-08-28-2 |
出現コレクション: | 学術雑誌掲載論文等 |
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