論文

査読有り 本文へのリンクあり
2018年8月

Lactosylceramide synthases encoded by B4galt5 and 6 genes are pivotal for neuronal generation and myelin formation in mice

PLoS Genetics
  • Toru Yoshihara
  • ,
  • Hiroyuki Satake
  • ,
  • Toshikazu Nishie
  • ,
  • Nozomu Okino
  • ,
  • Toshihisa Hatta
  • ,
  • Hiroki Otani
  • ,
  • Chie Naruse
  • ,
  • Hiroshi Suzuki
  • ,
  • Kazushi Sugihara
  • ,
  • Eikichi Kamimura
  • ,
  • Noriyo Tokuda
  • ,
  • Keiko Furukawa
  • ,
  • Koichi Fururkawa
  • ,
  • Makoto Ito
  • ,
  • Masahide Asano

14
8
開始ページ
e1007545
終了ページ
記述言語
掲載種別
研究論文(学術雑誌)
DOI
10.1371/journal.pgen.1007545

© 2018 Yoshihara et al. http://creativecommons.org/licenses/by/4.0/. 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.

リンク情報
DOI
https://doi.org/10.1371/journal.pgen.1007545
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30114188
Scopus
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85053085983&origin=inward 本文へのリンクあり
Scopus Citedby
https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85053085983&origin=inward
ID情報
  • DOI : 10.1371/journal.pgen.1007545
  • ISSN : 1553-7390
  • eISSN : 1553-7404
  • PubMed ID : 30114188
  • SCOPUS ID : 85053085983

エクスポート
BibTeX RIS