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Basic spproaches for gene therapy of hemoglobinopathy

Research Project

Project/Area Number 08457629
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Human genetics
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

FUKUMAKI Yasuyuki  Kyushu University, Institute of Genetic Information, Professor, 遺伝情報実験施設, 教授 (90128083)

Co-Investigator(Kenkyū-buntansha) IWAKI Akiko  Kyushu University, Institute of Genetic Information, Assistant Professor, 遺伝情報実験施設, 助手 (30253454)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1996: ¥4,400,000 (Direct Cost: ¥4,400,000)
Keywordsgene therapy / globin gene / thalassemia / AAV / insulator / HbE / antisense / splicing / アンセンチ / 赤芽球 / 転写
Research Abstract

(1) Position-independent expression of transgenes in target cells is one of essential subjects for successful gene therapies. We prepared recombinant adeno-associated virus (rAAV) containing the combination of the DNaseI hypersensitive site 2 (HS2), 3 (HS3), and 4 (HS4) core elements from the human beta-globin locus control region (LOR), the human beta-globin gene, and the herpes virus tymidine kinase promoter driven neomycin-resistant gene (neo^R) (rHS432, rHS43, rHS42, rHS32, and rHS2), and also rAAV containing two copies of the 250-bp core fragment of the chicken beta-globin insulator on both sides of the rHS2 (rlns/HS2/2Ins). After isolating neomycin resistant mouse erythroleukemia (MEL) cells infected with each rAAV, we analyzed structure of proviral genome of rAAV and determined expression level of the human beta-globin gene. The high variability of the expression level was observed among clones infected with recombinant virus lacking the insulator. In contrast, in the clones inf … More ected with rIns/HS2/lns, the range of expression of the human beta-globin gene was from 52.8% to 58.3% of the mouse beta-major globin gene. Thus, these results indicate that the insulator dramatically functioned to reduce the variability oftransgene expression due to the position effect. This insulator-rAAV vectorsystem is a promising way to provide the constant level of the transgene expression for gene therapy regardless of insertion sites in chromatin.
(2) Hemoglobin (Hb) E is the most common Hb variant among Southeast Asian populations. The mutation in codon 26 (GAG to AAG) of the beta-globin gene (beta^E) induces an alternative splicing, resulting in production of normally and aberrantly spliced beta-globin mRNA.Compound heterozygotes for beta-thalassemia and beta^E have a severe beta-thalassemia- disease. Repression of aberrant splicing due to the BE mutation could ameliorate severity of such patients. We showed that the aberrant splicing was partially repressed in the cells treated with antisense oligoribonucleotide targeted to the aberrant 5 splice site. Maximum effect of the antisense oligoribonucleotide was observed at concentration of 0.4 muM and 36 hrs after the treatment in our experiment. We also analyzed the effect of transient and stable expression of SF2/ASF on aberrant splicing in cells expressing the beta^E-globin gene. Partial repression of the aberrant splicing was also observed in both expression systems. These results imply that antisense oligoribonucleotide treatment and SF2/ASF expression are possible therapeutic applications for beta-thalassemia/HbE disease. Less

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (72 results)

All Other

All Publications (72 results)

  • [Publications] Manabe,J.et al.: "Two novel mutations in the reduced nicotinamide adenine dinucleotide(NADH)-cytochrome b5 reductase gene of a patinet with generalized type,hereditary methemoglobinemia." Blood. 88. 3208-3215 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sumimoto,H.et al.: "Assembly and activation of the phagocyte NADPH oxidase." J.Biol.Chem.271. 22152-22158 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ogawa,T.,et al.: "Accelerated evolution of snake venom phospholipase A2 isozymes for aquisition of diverse physiological functions." Toxicon. 34. 1229-1236 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nobuhisa,I.et al.: "Accelerated evolution of Trimeresurus okinavensis venom gland phopholipase A2 isozyme-encoding genes." Gene. 172. 267-272 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Deshimaru,M.,et al.: "Accelerated evolution of crotalinae snake venom gland serine proteases." FEBS Letters. 397. 83-88 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sriroongrueng,W.et al.: "Analysis of β-thalassemia mutations and β-locus control region hypersensitive sites 2,3 and 4 in Southern Thailand." Asian J.Trop.Med.Pub.Health. 28. 120-127 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fucharoen,S.et al.: "Molecular and hematological characterization of Hb Tak and Hb Pyrgos in Thailand." Southweast Asian J.Trop.Med.Pub.Health. 28. 110-114 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Iwaki,A.et.al.: "Identification and characterization of the gene encoding a new member of the α-crystallin/small hsp family, closely linked to the αB-crystallin gene in a head-to-head" Genomics. 45. 386-394 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nobuhisa,I.et al.: "Characterization and evolution of a gene encoding a Trimeresurus flavoviridis serm protein that inhibits basic phosphlipase A2 jsozymes in the snake's venom." Eur.J.Biochem.249. 838-845 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kamakura,S.,et al.: "Cloning and characterization of tha 5'-flanking region of the human dopamine D4 receptor gene." Biohem.Biophys.Res.Commun.235. 321-326 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohba,Y.et al.: "β-Thalassemia mutations in Japanese and Koreans." Hemoglobin. 21. 191-200 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nobuhisa,I.et al.: "Structures of gene encoding phospholipase A2 inhibitors from the serum of Trimeresurus flaviridis snake." Gene. 191. 31-37 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Furuya,H.et al.: "Adult onset globoid cell leukodystrophy(Krabbe disease): analysis of galactosylceramidase cDNA from four Japanese patients." Hum.Gnenet.100. 450-456 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Furuumi,H.et al.: "Molecular basis of β-thalassemia in the Maldives." Hemoglobin. 22. 141-151 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanphaichitr,V.et al.: "Type I and II hereditary methemoglobinemia due to NADH-cytochrome b5 reductase deficiency in Thai patients." Internal Medicine. 13. 81-85 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nobiuhisa,I.et al.: "Structural elements of Trimeresurusflaviridis serum inhibitors for recognition of its venome phospholipase A2 isozymes." FEBS Letters. 429. 385-389 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamada,M.et al.: "Thrombopoietin supports in vitro erythroid differentiation via its specific receptor c-MpI in a human leukemia cell line." Cell Growth & Differentiation. 9. 487-496 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nobuhisa,I.et al.: "Retrotramsposable CR1-like elements in crotalinae sanke genomes." Toxicon. 36. 915-920 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mizuki,K.et al.: "Functional modules and expression of mouse p40^<phox> and p65^<phox>, SH3-domain-cotaining proteins involved in the phagocyte NADPH oxidase complex." Eur.J.Biochem.251. 573-582 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mamiya,K.et al.: "Association of polymorphisms in the cytochrome P450(CYP)2C19 and 2C18 genes in Japanese epileptic patients." Pharmacogenetics. 8. 87-90 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsumoto,M.et al.: "High pressure induces G2 arrest in murine erythroleukemia cells." J.Biochem.123. 87-93 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Higasa,K.et al.: "Molecular basis of hereditary methemoglbinemia types,I and II." Brt.J.Haematol.103. 922-930 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Inoue,T.et al.: "Position-independent human β-globin gene expression mediated by a recombinant adeno-associated virus vector carrying the chicken β-globin insulator." J.Hum.Genet.印刷中. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hamamura,M.et al.: "Differential dicreases in c-fos and aldolase C mRNA expression in the rat cerebellum after repeated methamphetamine administration." Mol,Brain Res.印刷中. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 服巻保幸: "グロビン遺伝子 「赤血球」" 藤井寿一編 医学書院, 114-127 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Manabe, J., Roopen, A., Sumimoto, H., Yubisui, T., Bellingham, A.J., Layton, D.M.and Fukumaki, Y: "Two novel mutations in the reduced nicotinamide adenine dinucleotide (NADH)-cytochromeb5 reductase gene of a patinet with generalized type, hereditary methemoglobinemia." Blood. 88. 3208-3215 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sumimoto, H., Hata, K., Mizuki, K., Ito, T., Kage, Y., Sakaki, Y., Fukumaki, Y., Nakamura, M.and Takeshige, K.: "Assembly and activation of the phagocyte NADPH oxidase." J.Biol.Chem.271. 22152-22158 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ogawa, T., Nakashima, K., Nobuhisa, I., Deshimaru, M., Shimohigashi, Y., Fukumaki, Y., Sakaki, Y., Hattori, S.and Ohno, M.: "Accelerated evolution of snake venom phospholipase A2 isozymes for aquisition of diverse physiological functions." Toxicon. 34. 1229-1236 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nobuhisa, I., Nakashima, K., Deshimaru, M., Ogawa, T., Shimohigashi, Y., Fukumaki, Y., Sakaki, Y., Hattori, S., Kihara, H.and Ohno, M.: "Accelerated evolution of Trimeresurus okinavensis venom gland phopholipase A2 isozyme-encoding genes." Gene. 172. 267-272 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Deshimaru, M., Ogawa, T., Nakashima, K., Nobuhisa, I., Chijiwa, T., Shimohigashi, Y., Fukumaki, Y., Niwa, M., Yamashina, I., Hattori, S.and Ohno, M.: "Accelerated evolution of crotalinae snake venom gland serine proteases." FEBS Letters. 397. 83-88 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sriroongrueng, W., Schleiemacher, E., Panich, V., Nopparatana, C., Saechan, V., Laosombat, V., Pornpatkul, M.and Fukumaki, Y.: "Analysis of beta-thalassemia mutations and beta-locus control region hypersensitive sites 2,3 and 4 in Southern Thailand." Southeast Asian J.Trop.Med.Pub.Health. 28. 120-127 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fucharoen, S., Fucharoen, G., Sae-ung, N., Sanchaisuriya, K.and Fukumaki, Y.: "Molecular and hematological characterization of Hb Tak and Hb Pyrgos in Thailand." Southweast Asian J.Trop.Med.Pub.Health. 28. 110-114 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Iwaki, A., Nagano, T., Nakagawa, M., Iwaki, T.and Fukumaki, Y.: "Identification and characterization of the gene encoding a new member of the alpha-crystallin/small hsp family, closely linked to the alphaB-crystallin gene in a head-to-head manner." Genomics. 45. 386-394 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nobuhisa, I., Inamasu, S., Nakai, M., Tatsui, A., Mimori, T., Ogawa, T., Shimohigashi, Y., Fukumaki, Y., Hattori, S.Kihara, H.and Ohno, M.: "Characterization and evolution of a gene encoding a Trimeresurus flavoviridisserm protein that inhibits basic phosphlipase A2 isozymes in the snake's venom." Eur.J.Biochem.249. 838-845 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kamakura, S., Iwaki, A., Matsumoto, M.and Fukumaki, Y.: "Cloning and characteriztion of the 5'-flanking region of the human dopamine D4 receptor gene." Biochem.Biophys.Res.Commun.235. 321-326 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohba, Y.Hattori, Y., Harano, T., Harano, K., Fukumaki, Y., Ideguchi, H., Cho, H.I.and Park, S.S.: "beta-Thalassemia mutations in Japanese and Koreans." Hemoglobin. 21. 191-200 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nobuhisa, I.and Deshimaru, M., Chijiwa, T., Nakashima, K., Ogawa, T., Shimohigashi, Y., Fukumaki, Y., Hattori, S.Kihra, H.and Ohno, M.: "Structures of genes encoding phospholipase A2 inhibitors from the serum of Trimeresurus flaviridis snake." Gene. 191. 31-37 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Furuya, H., Kukita, Y., Nagano, S., Sakai, Y., Yamashita, Y., Fukuyama, H., Inatomi, Y., Saito, Y., Koike, R., Tsuji, S., Fukumaki, Y., Hayashi, K.and Kobayashi, T.: "Adult onset globoid cell leukodystrophy (Krabbe disease) : analysis of galactosylceramidase cDNA from four Japanese patients." Hum.Gnenet. 100. 450-456 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Furuumi, H., Firdous, N., Inoue, T., Ohta, H., Winichagoon, P., Fucharoen, S.and Fukumaki, Y.: "Molecular basis of beta-thalassemia in the Maldives." Hemoglobin. 22. 141-151 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanphaichitr, V., Mahasandana, C., Pung-amritt, P., Veerakul, G., Kankirawatana, S., Suvatte, V., Tritilanunt, S.and Fukumaki, Y.: "Type I and II hereditary methemoglobinemia due to HADH-cytochrome b5 reductase deficiency in Thai patients." Internal Medicine. 13. 81-85 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nobiuhisa, I., Chiwata, T., Fukumaki, Y., Hattori, S., Shimohigashi, Y.and Ohno, M.: "Structural elements of Trimeresurus flaviridis serum inhibitors for recognition of its venome phospholipase A2 isozymes." FEBS Lettrs. 429. 385-389 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamada, M., Komatsu, N., Kirito, K., Kashii, Y., Tomizuka, H., Okada, K., Endo, T., Fukumaki, Y., Shinjo, K., Abe, K.and Miura, Y.: "Thrombopoietin supports in vitro erythroid differentiation via its specific receptor c-MpI in a human leukemia cell line." Cell Growth & Differentiation. 9. 487-496 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nobuhisa, I., Ogawa, T., Deshimaru, M., Chijiwa, T., Nakashima, K., Chuman, Y., Shimohigashi, Y., Fukumaki, Y., Hattori, and Ohno, M.: "Retrotramsposable CR1-like elemnts in crotalinae sanke genomes." Toxicon. 36. 915-920 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mizuki, K., Kadomatsu, K., Hata, K., ito, T., Fan, Q., Kage, Y., Fukumaki, Y., Sakaki, Y., Takeshige, K.and Sumimoto, H.: "Functional modules and expression of mouse p40^<phox> and p65^<phox> SH3-domain-containing proteins involved in the phagocyte NADPH oxidase complex." Eur.J.Biochem.251. 573-582 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mamiya, K., Ieiri, I., Miyahara, S., Imai, J., Furuumi, H., Fukumaki, Y., Ninomiya, H., Tashiro, N., Yamnada, H.and Higuchi, S.: "Association of polymorphisms in the cytochrome P450 (CYP) 2C19 and 2C18 genes inn Japanese epileptic patients." Pharmacogenetics. 8. 87-90 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsumoto, M., Yamaguchi, T., Fukumaki, Y., Yasunaga, R.and Terada, S.: "High pressure induces G2 arrest in murine erythroleukemia cells." J.Biochem.123. 87-93 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Higasa, K., Manabe, J., Yubisui, T., Sumimoto, H., Amritt, P., Tanpahichitr, V., Fukumaki, Y.: "Molecular basis of hereditary methemoglbinemia types, I and II." Brt.J.Haematol. 103. 922-930 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Inoue, T., Yamaza, H., Sakai, Y., Mizuno, S., Ohno, M., Hamasaki, N., Fukumaki, Y.: "Position-independent human beta-globin gene expression mediated by a recombinant adeno-associated virus vector carrying the chicken beta-globin insulator." J.Hum.Genet.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hamamura, M., Ozawa, H., Kimuro, Y., Higasa, K., Iwaki, A., Fukumaki, Y.: "Differential dicreases in c-fos and aldolase C mRNA expression in the rat cerebellum after repeated methamphetamine administration." Mol.Brain Res.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Furumi,H.et al.: "Molecularbasis of β-thalassemia in the Maldives." Hemoglobin. 22. 141-151 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tanphaichitr,V.et al.: "Type I and II herekitary methemoglobinemia due to NADH-cytochromeb5 reductase deficiencyin Thai patients." Internal Medicine. 13. 81-85 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nobiuhisa,I.et al.: "Structural elements of Trimeresurus flaviridis serum inhibitors for recognition of its venome phospholipase A2 isozymes." FEBSLetters. 429. 385-389 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamada,M.et al.: "Thrombopoietin supports in vitroerythroid differentiation via its specific receptor c-MpIin a human leukemia cell line." Cell Growth & Differentiation. 9. 487-496 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nobuhisa,I.et al.: "Retrotramsposable CR1-like elements incrotalinae sanke genomes." Toxicon. 36. 915-920 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mizuki,K.et al.: "Functional modules and expression of mouse p40^<pbox> and p65^<pbox>,SH3- domain-containing proteins involved in the phagocyte NADPH oxidase complex." Eur.J.Biochem.251. 573-582 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mamiya,K.et al.: "Association of polymorphisms in the cytochrome P450(CYP)2C19 and 2C18 genes inn Japanese epileptic patients." Pharmacogenetics. 8. 87-90 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Matsumoto,M.et al.: "High preeure induces G2 arrest in murine eryghroleukemia cells." J.Biochem.123. 87-93 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Higasa,K.et al.: "Molecularbasis of hereditary methemoglbinemia types,I and II." Brt.J.Haematol.103. 922-930 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Inoue,t.et al.: "Position-independent human β-globingene expression mediated by a recombinantadeno-associated virus vector carrying thechicken β-globin insulator." J.Hum.Genet.(印刷中). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hamamura,M.et al.: "Differential diceases in c-fos and aldolase C mRNA expression in the ratcerebellum after repeated methamphetamineadministration." Mol.Brain Res.(印刷中). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 服巻保幸: "グロビン遺伝子「赤血球」" 藤井寿一編 医学書院, 114-127 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Ohba et al.: "Thalassemia mutations in Japanese and Koreans" Hemoglobin. 21・2. 191-200 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kamakura et al.: "Cloning and characterization of the 5′-flanking region of the human dopamine D4 receptor gene." Biochemical and Biophysical Research Communications flavoiridis Snake.235. 321-326 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nobuhisa,I.et al.: "Structures of genes encoding phopholipase A2 inhibitors from the serum of Trimeresurus" Gene. 191. 31-37 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Furuya,H.et al.: "Adult onset globoid cell leukodystrophy(Krabbe disease):analysis of galactosylceramidase cDNA from four Japanese patients." Human Genetics. 100. 450-456 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Iwaki,A.et al.: "Identification and characterization of the gene encoding a new member of the αB-crystallin/small hasp family,closely liked to the αB-crystallin gene in a head-to-head manner." Genomics. 45. 386-394 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nobuhisa,I.et al.: "Characteruzation and evolution of a gene encding a Trimeresurus flaviridis serum protein that inhibits basic phospholipase A2 isozymes in the snake's venom." European Journal of Biochemistry. 249. 838-845 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nobuhisa,I.et al.: "Accelerated evolution of Trimeresurus okinavensis venom gland phosphlipase A2 isozyme-encoding genes" gene. 172. 267-272 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sumimoto,H.et al.: "Assembly and activation of the phagocyte NADPH oxidase" The Journal of Biological Chemistry. 271・36. 22152-22158 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Manabe,J.et al.: "Two novel mutations in the reduced nicotinamide adenine dinucleotide(NADH)-cytochrome b5 reductase gene of a patient with generalized type,hereditary methemoglobinemia" Blood. 88・8. 3208-3215 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Deshimaru,M.et al.: "Accelerated evolution of crotalinae snake venome gland serine protease" FEBS Letter. 397. 83-88 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 服巻 保幸: "グロビン遺伝子の発現ならびに制御とその病態" 日本臨床. 54・9. 2311-2319 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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