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Gene Therapy for Genetic Neurodegenerative Disorders by Cultured Microglia Cell for Gene Delivery

Research Project

Project/Area Number 11694306
Research Category

Grant-in-Aid for Scientific Research (A).

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionOsaka City University Graduate School of Medicine

Principal Investigator

TANAKA Akemi  Osaka City University Graduate School of Medicine, Department of Pediatrics, Associate Professor, 医学部, 助教授 (30145776)

Co-Investigator(Kenkyū-buntansha) FUKAI Kzuyoshi  Osaka City University Graduate School of Medicine, Department of Dermatology, Associate Professor, 医学部, 助教授 (20244642)
OTANI Shuzo  Osaka City University Graduate School of Medicine, The 2nd Department of Biochemistry, Professor, 医学部, 教授 (80047068)
SATO Makoto  Fukui Medical School, The 2nd Department of Anatomy, Professor, 医学部, 教授 (10222019)
MAEDA Mitsuyo  Osaka City University Graduate School of Medicine, The 1st Department of Anatomy, Lecturere, 医学部, 講師 (40122080)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥11,300,000 (Direct Cost: ¥11,300,000)
Fiscal Year 2000: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1999: ¥6,300,000 (Direct Cost: ¥6,300,000)
KeywordsMICROGLIA CELL / ADENOVIRUS VECTOR / LYSOSOMAL STORAGE DISEASE / β-GLUCURONIDASE DEFICIENCY / GENE EXPRESSION / GFP
Research Abstract

Gene delivery into the brain via blood vessels is quite difficult because of the blood-brain-barrier (BBB). It is speculated that microglia cells would go through BBB.We established a strain of cultured microglia cell from newborn mice brain for the vehicle of gene into the brain. The cells were labeled with a reporter gene of GFP and injected into the left ventricle of heart of Sly mice. Sly mouse, the deficiency of β-glucuronidase, is a mouse model for human disease of mucopolys accharidosis type VII, which is a systemic disorder including the brain caused by the accumulation of glycosaminoglycans. It is suggested that delivery of the deficient enzyme or the gene into each organ would improve the disease.
In the literature, a number of experiments of gene therapy for the brain have been done, but none of them has not been successful. In our study, the cultured microglia cells could enter the brain tissue via blood vessel only when BBB was injured by the disease progression, but they do not go through normal BBB.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (43 results)

All Other

All Publications (43 results)

  • [Publications] Seto T,Kono T et al.: "Brain MRI in 23 patients with mucopolysaccharidoses and the effect of BMT."Ann.Neurol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagano T,Nakamura A et al.: "A2-Pancortins (Pancortin-3 and -4) are the dominant Pancortins during neocortical development."J.Nerochem.. 75. 1-8 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Saitoh S,Oiso N et al.: "Oculocutaneous albinizm type 2 with a P gene missence mutation in a patient with Angelman syndrome"J.Ned.genet.. 37・5. 392-394 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yagi T,Jikihara I et al.: "Rescue of ischemic brain injury by adenoviral gene trasfer of glial cell -line derived neutropenic factor after transient global ischemia in gerbils."Brain Res.. 885. 273-282 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Oya Y,Proia RL et al.: "Distribution of enzyme-bearing cells in GM2 gangliosidosis nice : regionally specific pattern of cellular infiltration following bone marrow transplantation."Acta Neuropathol.. 99. 161-168 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wu YP,Matsuda J et al.: "Infiltration of hematogenous lineage cells into the demyelinating central nervous system of twitcher mice."J.Neurophath.Exper.Neurol.. 59. 628-639 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wenger DA,Suzuki K et al.: "The Metabolic and Molecular Bases of Inherited Disease"McGraw-Hill. New York. 6338 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tanaka A, Fujimaru M, Choeh K, Isshiki G: "Novel mutations including the second most common in Japan in the β-hexosaminidase α subunit gene, and a simple screening of Japanese patients with Tay-Sachs disease."J.Hum.Genet.. 41. 91-95 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yamamoto T, Nanba E, Ninomiya H, Higaki K, Taniguchi M, Zhang H, Inui K, Okada S, Tanaka A, Sakuragawa N, Millat G, Vanier MT, Morris JA, Pentchev PG, Ohno K.: "NPC1 gene mutations in Jaspanese patients with Niemann-Pick disease type C."Hum.Genet.. 104. 10-16 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sakai Y, Kiyotani K, Fukumura M, Asakawa M, Kato A, Shoda T, Yoshida T, Tanaka A, Hasegawa M, Nagai Y: "Accomodation of forigin genes into the Sendai virus genome : sizes of inserted genes and vial replication."FEBS Lett.. 456. 221-226 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Seto T, Kono T, Morimoto K, Inoue Y, Shintaku H, Hattori H, Matsuoka O, Yamano T, and Tanaka A: "Brain MRI in 23 patients with mucopolysac charidoses and the effect of BMT."Ann.Neurol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Suzumori N, Sato M, yoneda T, Ozaki Y, Takagi H, Suzumori K: "Expression of secretory leukovyte protease inhibitor in ovarian endometriomas and eutopic endometrium of womenn with endometriosis."Fetil.Steril.. 72. 857-867 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ijichi H, Tanaka T, Nakamura T, Nakamura T, Yagi H, Hakuba A, Sato M: "Molecular cloning and characterization of a human homologue of TBPIP, a BRCA1 locus-related gene."Gene. 248. 99-107 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagano T, Nakamura A, Konno D, Kurata M, Yagi H, Sato M: "A2-Pancortins (Pancortin-3 and -4) are the dominant Pancortins during neocortical development."J.Neurochem.. 75. 1-8 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Keng VW, Yagi H, Ikawa M, Nagano T, Myint Z, Yamada K, Tanaka T, Sato A, Muramatsu I, Okabe M, Sato M, Noguchi T: "Homeobox gene Hex is essential for onset of mouse embrionicliver development."Biochem.Biophys.Res.Commun.. 1276. 1155-1161 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kimura M, Tanabe K, Krishna S, Tsuboi T, Saito-Ito A, Otani S, Ogura H: "Gametocyte-dominant expression of a novel P-type ATPase in Plasmodium yoelii."Mol.Biochem.Parasitol.. 104. 331-336 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsukamoto T, Kinoshita H, Hirohashi K, Kubo S, Tanaka h, Otani S: "Human erythrocyte polyamine levels after portal vein embolism."Hepato-Gastroenterol.. 46. 3178-3183 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tachibana A, Yano Y, Otani S, Nomura N, Sako Y, Taniguchi M: "Novel prenyltransferase gene encoding farnesylgeranyl diphosphate synthetase from a hyperthermophilic archaeon, Aeropyrum pernixx-Molecular evolution with alteration in product specificity."Eur.J.Biochem.. 267. 321-328 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kageyama K, Yamada R, Otani S, Onoyama Y, Yano I, Yamaguchi W, Yamaguchi Y, Kogawa H, Nagao N, Miwa N: "Cytotoxity of docosahexaenoic acd and eicosapentaenoic acid in tumor cells and the dependence on binding to serum proteins and incorporation into intracellular lipids."Oncol.Reports.. 7. 79-83 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tosaka Y, Tanaka H, Yana Y, Masai K, Nozaki M, Yomogida K, Otani S, Nojima H, Nishimune Y: "Identification and characterization of testis specific ornithine decarboxylase antizyme (OAZ-t) gene : expression in haploid germ cells and polyamine-induced frameshifting."Genes to Cells.. 5. 265-276 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kubo S, Tamori A, Omura T, Ikebe T, Wakasa K, Hirohashi K, Kinoshita H, Otani S: "Ornithine decarboxylase activity in the non-cancerous hepatic tissue of patients with hepatocellular cartinoma."Hepato-Gastroenterol. 47. 820-823 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masuda C, Wanibuchi H, Sekine K, Yano Y, Otani S, Kishimoto T, Tsuda H, Fukushima S: "Chemopreventive effects of bovine lactoferrin on N-butyl-N-(4-hydroxybutyl) nitrosamine-induced rat bladder cartinogenesis."Jap.J.Cancer Res.. 91. 582-588 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nishiguchi S, Enomoto M, Shiomi S, Tanaka M, Fukuda K, Tamori A, Tanaka T, Takeda T, Seki S.Yano Y, Otani S, Kuroki T: "TT virus infection in patients with chronic liver disease of unknownn etiology."J.Med.Virol.. 62. 392-389 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Oiso N,Fukai K, Ishi M: "Interleukin 4 receptor α chain polymorphism Gln551Arg is associated with adult atopic dermatitis in Japan."British J.Dermatol.. 142. 1003-1006 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Saitoh S, Oiso N, Wada T, Narazaki O, Fukai K: "Oculocutaneous albinism type 2 with a P gene missence mutation in a patient with Angelman syndrome."J.Med.Genet.. 37. 392-394 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Richards KA, Fukai K, Oiso N, Paller AS: "A novel KIT mutation results in piebaldism with progressive depigmentation."J.Am.Acd.Dermatol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yagi T, Jikihara I., Fukumura M., Watabe K., Ohashi T., Eto Y., Hara M., Maeda M.: "Rescue of brain injury by adenoviral gene transfer of glial cell line-drived neurotrophic factor after transient global ischemia in gerbils."Brain Res.. 885. 273-282 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yamanaka S., Zhang X.Y., Maeda M., Farese RV.Jr., Iwao H.: "Innerarity L Essential role of NAT1/p97/ in embrionic differenciation and the retinoic pathway."EMBO J.. 19. 5533-5541 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoneda T, Imaizumi K, Maeda M, Yui D, Manabe T, Katayama T, Sato N, Gomi F, Morihara T, Mori Y, Miyoshi K, Hitomi J, Ugawa S., Yamada S, Okabe M., Tohyama M: "Regulatory mechanisms of TRAF2-mediated signal transduction by BcL10, a MALT lymphoma-associated protein."J.Biol.Chem.. 275. 11114-11120 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hayashi Y, Jikihara I, Yagi T, Fukumura M, Ohhashi Y, Ohta Y, Takahi H, Maeda M: "Immunohistochemical investigation of caspase-1 and effect of caspase-1 inhibitor in delayed neuronal death after transient cerebral ischemia."Brain Res.. 893. 113-120 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Seto T,Kono T et al.: "Brain MRI in 23 patients with mucopolysaccharidoses and the effect of BMT."Ann.Neurol. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Nagano T,Nakamura A et al.: "A2-Pancortins (Pancortin-3 and -4) are the dominant Pancortins during neocortical development."J.Nerochem.. 75. 1-8 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Saitoh S,Oiso N et al.: "Oculocutaneous albinizm type 2 with a P gene missence mutation in a patient with Angelman syndrome"J.Ned.genet.. 37・5. 392-394 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yagi T,Jikihara I et al.: "Rescue of ischemic brain injury by adenoviral gene trasfer of glial cell-line derived neutropenic factor after transient global ischemia in gerbils."Brain Res.. 885. 273-282. (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Oya Y,Proia RL et al.: "Distribution of enzyme-bearing cells in GM2 gangliosidosis nice : regionally specific pattern of cellular infiltration following bone marrow transplantation."Acta Neuropathol.. 99. 161-168 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Wu YP,Matsuda J et al.: "Infiltration of hematogenous lineage cells into the demyelinating central nervous system of twitcher mice."J.Neurophath.Exper.Neurol.. 59. 628-639 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Wenger DA,Suzuki K et al.: "The Metabolic and Molecular Bases of Inherited Disease"McGraw-Hill. New York. 6338 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] A. Tanaka, M. Fujimaru et al.: "Novel mutations including the second most common in Japan in the β-hexosaminidase a subunit gene, and a simple screening of Japanese patients with Tay-Sachs diseae"Journal of Human Genetics. 44・1. 91-95 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T. Yamamoto, E. Nanba et al.: "NPC1 gene mutations in Japanese patients with Niemann-Pick disease type C"Hum. Genet.. 104・1. 10-16 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y. Sakai, K. Kiyotani et al.: "Accomodation of foriegn genes into the Sendai virus genome: sizes of inserted genes and viral replication"FEBS Lett.. 456. 221-226 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] N. Suzumori, M. Sato et al.: "Expression of secretory leukocyte protease inhibitor in ovarian endometriomas and eutopic endmetrium of woman with endometriosis"Fertil. Steril.. 72・5. 857-867 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H. Ijichi, T. Tanaka et al.: "Molecular cloning and characterization of humanhomologue of TBPIP, a BRCA1 locus-related gene"Gene. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] S. Saito, N. Oiso et al.: "Angelman syndrome plus oculocutaneus albinism type 2 associated with a P gene missence mutation"J. Med. Genet.. (in press).

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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