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2000 Fiscal Year Final Research Report Summary

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
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.

  • Research Products

    (30 results)

All Other

All Publications (30 results)

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

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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

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  • [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)

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  • [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)

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  • [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)

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  • [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).

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      「研究成果報告書概要(欧文)」より
  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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).

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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Published: 2002-03-26  

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