Biological roles of sulfated glycolipids and pathophysiology of their deficiency

硫酸化糖脂的生物学作用及其缺乏的病理生理学

基本信息

  • 批准号:
    14082204
  • 负责人:
  • 金额:
    $ 30.72万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research on Priority Areas
  • 财政年份:
    2002
  • 资助国家:
    日本
  • 起止时间:
    2002 至 2006
  • 项目状态:
    已结题

项目摘要

Glycolipid sulfotransferase (CST)-knockout (KO) mice manifest neurological disorders due to myelin dysfunction and an arrest of spermatogenesis, indicating that sulfatide and seminolipid are essential for myelin formation and spermatogenesis, respectively. The adhesion between the lateral loop of myelin sheath and the axolemmma at the nodes of Ranvier is deteriorated in CST-KO mice, resulting in deterioration of clustering of sodium and potassium channels. This defect occurs not at development but at maintenance process. In CST-KO mice, terminal differentiation and morphological maturation of oligodendrocytes are enhanced, indicating that sulfatide is a key molecule for the negative regulation of oligodendrocyte terminal differentiation. Transplantation of spermatogonia from the green mouse, in which green fluorescent protein is systemically expressed, revealed that defect of CST-KO mice is not in the Sertoli cells but in the germ cells. Seminolipid is found to be expressed on the plasma membranes of spermatogonia, spermatocytes, spermatids, and spermatozoa. Moreover, CST-deficiency ameliorates L-selectin-dependent monocyte infiltration in the kidney after ureteral obstruction, an experimental model of renal interstitial inflammation, indicating that sulfatide is an endogenous ligand of L-selectin. CST-KO mice were employed to raise a monoclonal antibodiy (MoAb) against sulfated glycolipids. We produced a recombinant single-chain variable-fragment (scFv) antibody based on the gene on the MoAb. Finally, we introduced the GP3ST gene, which is a member of the CST gene family, into human lung adnocarcinoma cells that highly express sialyl Lewis X antigen. As the result, the cancer cells turn to express sulfo Lewis X antigen instead of sialyl Lewis X antigen and tumor metastasis via blood vessels was suppressed by the expression of GP3ST gene.
糖脂磺基转移酶(CST)基因敲除(KO)小鼠表现出神经系统疾病,由于髓鞘功能障碍和精子发生的逮捕,表明硫苷脂和磷脂是必不可少的髓鞘形成和精子发生,分别。在CST-KO小鼠中,髓鞘的侧环与朗维尔结处的轴膜之间的粘附恶化,导致钠和钾通道的聚集恶化。该缺陷不是发生在开发过程中,而是发生在维护过程中。在CST-KO小鼠中,少突胶质细胞的终末分化和形态成熟增强,表明硫苷脂是负调控少突胶质细胞终末分化的关键分子。从全身表达绿色荧光蛋白的绿色小鼠中移植精原细胞,揭示了CST-KO小鼠的缺陷不是在支持细胞中,而是在生殖细胞中。发现精脂在精原细胞、精母细胞、精子细胞和精子的质膜上表达。此外,CST缺乏可改善输尿管梗阻后肾脏中L-选择素依赖性单核细胞浸润,这是肾间质炎症的实验模型,表明硫苷脂是L-选择素的内源性配体。采用CST-KO小鼠制备抗硫酸化糖脂的单克隆抗体(MoAb)。我们根据单克隆抗体上的基因制备了重组单链可变片段(scFv)抗体。最后,我们将CST基因家族的一员GP 3ST基因导入高表达唾液酸刘易斯X抗原的人肺腺癌细胞中。结果,癌细胞转而表达磺基刘易斯X抗原而不是唾液酸基刘易斯X抗原,并且通过血管的肿瘤转移被GP 3ST基因的表达抑制。

项目成果

期刊论文数量(70)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Dysregulation of TGF-β1 receptor activation leads to abnormal lung development and emphysema-like phenotype in core fucose-deficient mice
Honke, K. et al.: "Biological roles of sulfoglycolipids and pathophysiology of their deficiency"Glycoconj.J.. (印刷中). (2004)
Honke, K. 等人:“磺基糖脂的生物学作用及其缺陷的病理生理学”Glycoconj.J.(出版中)。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Decoding sugar functions by identifying target glycoproteias.
通过识别目标糖蛋白来解码糖功能。
Sulfatide is a negative regulator of oligodendrocyte differentiation: Development in sulfatide-null mice
  • DOI:
    10.1002/glia.10327
  • 发表时间:
    2004-02-01
  • 期刊:
  • 影响因子:
    6.2
  • 作者:
    Hirahara, Y;Bansal, R;Wada, Y
  • 通讯作者:
    Wada, Y
Ogawa, D. et al.: "Cerebroside sulfotransferase deficiency ameliorates L-selectin-dependent monocyte infiltration in the kidney after ureteral obstruction"J.Biol.Chem.. 279. 2085-2090 (2004)
Okawa, D. 等人:“脑苷磺基转移酶缺乏改善输尿管梗阻后肾脏中 L-选择素依赖性单核细胞浸润”J.Biol.Chem.. 279. 2085-2090 (2004)
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    0
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HONKE Koichi其他文献

HONKE Koichi的其他文献

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{{ truncateString('HONKE Koichi', 18)}}的其他基金

Identification of sialyl Lewis antigen carrier proteins involved in the metastasis of lung cancer and development of diagnostic method to measure them
鉴定参与肺癌转移的唾液酸Lewis抗原载体蛋白并开发测量它们的诊断方法
  • 批准号:
    25670166
  • 财政年份:
    2013
  • 资助金额:
    $ 30.72万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Bioinformation Produced by Molecular Interactions in The Membrane Microdomains
膜微域中分子相互作用产生的生物信息
  • 批准号:
    22659060
  • 财政年份:
    2010
  • 资助金额:
    $ 30.72万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Molecular Mechanisms to Regulate The Metabolism of Water and Electrolytes
调节水和电解质代谢的分子机制
  • 批准号:
    21390096
  • 财政年份:
    2009
  • 资助金额:
    $ 30.72万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Production of autoantibodies and an animal model of autoimmune disease using a knockoutmouse
使用基因敲除小鼠生产自身抗体和自身免疫性疾病动物模型
  • 批准号:
    15590271
  • 财政年份:
    2003
  • 资助金额:
    $ 30.72万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
SULFATED GLYCOLIPID THAT REGULATES DEVELOPMENT OF MALE GERM CELLS
调节雄性生殖细胞发育的硫酸糖脂
  • 批准号:
    13670138
  • 财政年份:
    2001
  • 资助金额:
    $ 30.72万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
MECHANISMS OF AUTONOMOUS PROLIFERATION OF HUMAN RENAL CANCER CELLS
人肾癌细胞自主增殖机制
  • 批准号:
    07671700
  • 财政年份:
    1995
  • 资助金额:
    $ 30.72万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

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生成一种新型条件敲除小鼠,用于控制细胞因子反应的超级增强子
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    10740932
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条件性ataxin-1基因敲除小鼠品系的开发
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体育锻炼对视网膜变性 Snf2h 基因敲除小鼠的神经保护作用
  • 批准号:
    466983
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    2021
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    $ 30.72万
  • 项目类别:
    Studentship Programs
The Jackson Laboratory Knockout Mouse Production and Phenotyping Project (JAX KOMP2)
杰克逊实验室基因敲除小鼠生产和表型项目 (JAX KOMP2)
  • 批准号:
    10386984
  • 财政年份:
    2021
  • 资助金额:
    $ 30.72万
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The Jackson Laboratory Knockout Mouse Production and Phenotyping Project (JAX KOMP2)
杰克逊实验室基因敲除小鼠生产和表型项目 (JAX KOMP2)
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Development of Microglia Knockout Mouse
小胶质细胞敲除小鼠的研制
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    2020
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Characterization of the prolactin inducible protein, PIP, knockout mouse model PIP KO-CRISPR
催乳素诱导蛋白 PIP、敲除小鼠模型 PIP KO-CRISPR 的表征
  • 批准号:
    540048-2019
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Neuroglobin in the Retina. Use of a Knockout Mouse for Functional assessment / Phenotyping and examining Human relevance, towards Neuroprotection.
视网膜中的神经球蛋白。
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转基因/基因敲除小鼠共享资源
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使用 Hoatzin 基因敲除小鼠研究脊椎动物活动纤毛发生
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  • 财政年份:
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