Study on neurological disorder caused by ganglioside-deficiency and therapeutics by glycolipid supplement
| Project/Area Number |
16H04681
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory animal science
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
吉原 亨 京都大学, 医学研究科, 特定助教 (00401935)
成瀬 智恵 京都大学, 医学研究科, 准教授 (30372486)
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| Research Collaborator |
Sugihara Kazushi
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2016: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
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| Keywords | ガングリオシド / LacCer合成酵素 / ガラクトース転移酵素 / 神経細胞 / 軸索 / ミエリン鞘 / 神経幹細胞 / 糖鎖 / 脳神経疾患 |
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| Outline of Final Research Achievements |
We clarified that B4galt5 and B4galt6 genes were responsible for Lactosylceramide (LacCer) synthase in the initial biosynthetic step of gangliosides abundantly present in the brain. Neuron-specific B4galt5 and B4galt6 double-deficient mice died before 4 weeks of age with growth retardation and ataxia. The ganglioside-deficiency caused immature neurons and reduced signal transduction through NGF. Furthermore, axonal and myelin formation were remarkably impaired in the spinal cord, resulting in motor ataxia. We could elucidate important functions of gangliosides in the nervous system.
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| Academic Significance and Societal Importance of the Research Achievements |
哺乳類の脳内には様々なガングリオシドが豊富に存在するが，ガングリオシドを完全に欠損させた場合の神経系に与える影響については不明な点が多かった。本研究でガングリオシドを欠損させたマウスを作製することに成功し，ガングリオシドの神経系での機能の一端を明らかにした。ヒトでも一部のガングリオシドが欠損したり，逆に異常に蓄積したりする疾患が知られているので，それらの病態解明や治療法の開発に有用なモデルマウスを開発できたと考えている。
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Report
(4 results)
Research Products
(7 results)
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[Journal Article] Lactosylceramide synthase, encoded by β4-galactosylteransferase-5 and -6, is pivotal for neuronal generation and myelin formation in mice.2018
Author(s)
Yoshihara T, Satake H, Nishie T, Okino N, Hatta T, Otani H, Suzuki H, Sugihara K, Kamimura E, Tokuda N, Furukawa K, Furukawa K, Ito M, Asano M.
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Journal Title
Plos Genetics
Volume: 14
Issue: 8
Pages: 1-24
DOI
Related Report
Peer Reviewed / Open Access
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