Generation of the mouse model of neuronopathic Gaucher diseasse aiming the development of new therapy for the neurological involvement
| Project/Area Number |
18591169
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Tokai University |
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Principal Investigator |
MATSUDA Junko Tokai University, Future Science and Technology Joint Research Center, Associate Professor (60363149)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Kunihiko Tokai University, Future Science and Technology Joint Research Center, Professor (30384895)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,970,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥570,000)
Fiscal Year 2007: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Gaucher disease / model mouse / saposin / sphingolipidosis / neuropathology |
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| Research Abstract |
Gaucher's disease (GD) is the most common lysosomal storage diseases, caused by a deficiency of the lysosomal enzyme, acid-β-glucosidase (Gcase). Gaucher's disease has three clinical subtypes: Type I (or nonneuropathic form), Type II (or acute infantile neuropathic form) and Type III (the chronic neuronopathic form). The incidence of neuronopathic form is relatively high in Japan. For Type I patients, enzyme replacement therapy is quite effective and has recently become the standard treatment. In contrast, there is currently no effective treatment for the severe brain damage that may occur in patients with Types II and III GD. In this study, we have tried to generate the mouse model of neuronopathic GD by knocking out the activator protein for Gcase, saposin C. We have introduced the specific mutation, which substitute 5th cystein to serine in the saposin C domain of mouse sphingolipid activator protein (prosaposin) gene. Saposin C knockout mice (Sap-C-/-) were born and grew normally. At around 3 months of age, Sap-C-/-were indistinguishable with their wild type littermates. However at around 6 months of age, Sap-C-/- began to show subtle neurological symptoms. Neuropathological evaluation at around 6 months of age showed at least the selective and dramatic loss of cerebellar Purkinje cells. Although more long term and detailed neuropathological analyses are necessary, Sap-C-/- could be the mouse model of Type III, the chronic neuronopathic form of GD.
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Report
(3 results)
Research Products
(29 results)
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[Journal Article] Combined saposin C and D deficiencies in mice lead to a neuronopathic phenotype, glucosylceramide and a-hydroxy ceramide accumulation, and altered prosaposin trafficking2007
Author(s)
Sun, Y., Witte, DP., Zamzow, M., Ran, H., Quinn, B., Matsuda, J., Grabowski, GA
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Journal Title
Human Molecular Genetics 16
Pages: 957-971
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] GD3-and O-acetylated GD3-ganglopsides in the GM2 synthase-deficient mouse brain and theii immunohistochemical localization2006
Author(s)
Matsuda, J., Vanier, MT., Popa, I., Portoukalian, J., Suzuki, K
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Journal Title
Proc. Jpn. Acad, Ser. B 82
Pages: 189-196
Description
「研究成果報告書概要(欧文)」より
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