1995 年度実績報告書

ヒトカテコールアミン生合成酵素遺伝子導入トランスジェニックマウスの組織化学的解析

研究課題

研究課題/領域番号	06454696
研究機関	藤田保健衛生大学
研究代表者	永津郁子藤田保健衛生大学, 医学部・解剖学, 教授 (80084573)
研究分担者	唐沢延幸藤田保健衛生大学, 医学部・解剖学, 研究員 (70148287) 酒井正雄藤田保健衛生大学, 医学部・解剖学, 講師 (90196048) 新井良八藤田保健衛生大学, 医学部・解剖学, 助教授 (20159487) 山田啓喜藤田保健衛生大学, 衛生学部・解剖学, 助教授 (60084604)
キーワード	カテコールアミン生合成酵素 / 遺伝子導入 / トランスジェニックマウス / 免疫組織化学 / ドーパミン / ノルアドレナリン / アドレナリン / セロトニン
研究概要	1)トランスジェニックマウス(Tgマウス)の脳の解析 1.1)ヒトのチロシン水酸化酵素(TH)のプロモーターと細菌のクロラムフェニコールアセチル転移酵素(CAT)の遺伝子との融合遺伝子を持つTgマウスの脳において、この導入遺伝子はカテコールアミン(CA)ニューロンに発現される(Sasaoka et al., Mol. Brain Res,.16:274,1992)ほか、異所性にCAニューロン以外のニューロンにも発現される(Nagatsu, l. et al., J. Neural Transm., 96:85,1994)。我々は電顕免疫組織化学を用いて、このTgマウスのド-バミンニューロンの細胞体、樹状突起(中脳腹側被蓋野)および神経線維終末(扁桃体中心核)にCAT蛋白が存在すること(Arai et al., Neurosci. Lett.,168:76,1994)、また異所性ニューロンに発現されるCAT蛋白に関しても、歯状回の顆粒細胞の細胞体、樹状突起および神経線維終末にその局在を認めた(Arai et al.,1995 in press)。CAニューロンおよび異所性ニューロンに発現したCAT蛋白は、軸索輸送にて神経線維終末まで運ばれることが示唆される。 1.2)ヒトのド-バミン-β-水酸化酵素(DBH)のプロモーターとヒトのフェニールエタノールアミン-N-メチル転移酵素の遺伝子(hPNMT)との融合遺伝子を持つTgマウス(Kobayashi et al., Proc. Natl. Acad.Sci. USA,89:1631、1992)の脳において、ニューロンに発現された導入遺伝子の発現産物が神経線維終末まで運ばれることを示唆する結果を得た(Arai et al., Brain Res.621:141,1993)。Tgマウスの特定のニューロンに、特定の生理活性物質の合成酵素またはペプチドを発現させることによって、そのニューロンの神経線維終末までこれらが運ばれる可能性がある。 1.3)ヒトのTHのプロモーターは同じで、レポーター遺伝子(CATあるいはhPNMT)を変えても、ドーパミンとアドレナリンニューロンには発現するが、ノルアドレナリンニューロンには発現しない(Yamada et al., Biogenic Amines 11:339,1995)。レポーター遺伝子(hPNMT)は同じで、THのプロモーターのかわりにDBHのプロモーターを用いると、ドーパミンニューロンには発現しないが、ノルアドレナリンとアドレナリンニューロンに発現する。 2)ラットの脳の解析 2.1)腹腔内投与のL-DOPAは、ドーパミンニューロンの他にセロトニンニューロンの細胞体(背側縫線核)(Arai et al., Brain Res.667:295,1994)、及びセロトニンの神経終末(線条体)(Arai et al., Neurosci. Lett.195:195.1995)でも取り込まれてドーパミンになる。 2.2)腹腔内投与の5-ハイドロキシトリプトファンは、セロトニンニューロンの他にドーパミンニューロンの細胞体(黒質)やノルアドレナリンニューロンの細胞体(青斑核)に取り込まれてセロトニンになる(Arai ei al., Brain Res.669:145,1995)。

研究成果

(22件)

すべてその他

すべて文献書誌 (22件)

[文献書誌] Y. Ichitani, H. Okamura, D. Nakahara, I. Nagatsu, Y. Ibata.: "Biochemical and immunocytochemical changes induced by intrastriatal 6-hydroxydopamine injection in the rat nigrostriatal dopamine neuron system: evidence for cell death in the substantia nigra." Experimental Neurology. 130. 269-278 (1994)
[文献書誌] R. Arai, D. M. Jacobowitz, I. Nagatsu: "Up- tegulation of calretinin inthe supraoptic nucleus of the rat after chronic salt loading." Brain Res.673. 339-343 (1995)
[文献書誌] R. Arai, N. Karasawa, M. Geffard, I. Nagatsu.: " L- Dopa is converted to dopamine in serotonergic fibers of the striatum of the rat:a double- labeling immunofluorescence study." Neurosci. Lett.195. 195-198 (1995)
[文献書誌] R. Arai, N. Karasawa, T. Nagatsu, I. Nagatsu.: "Exogenous L-5-hydroxytryptophan is decarboxylated in neurons of the substantia nigra pars compacta and locus coeruleus of the rat." Brain Res.669. 145-149 (1995)
[文献書誌] R. Arai, K. Satoh, K. Kitahama, H. Ohshima, I. Nagatsu.: "Ultrastructural localization of nitric oxide synthase immunoreactivity in the frontal cortex of the monkey.21GC05:Biogenic Amines" 11(5). 409-415 (1995)
[文献書誌] N. Karasawa, R. Arai, G. Isomura, T. Nagatsu, I. Nagatsu.: "Chemical features of monoaminergic and non-monoaminergic neurons in the brain of laboratory shrew(Suncus murinus)are changed by systemic administration of monoamine precursors." Neuroscience Research. 24(1). 67-74 (1995)
[文献書誌] H. Kawano, K. Ohyama, K. Kawamura, I. Nagatsu.: "Migration of dopaminergic neurons in the embryonic mesencephalon of mice." Developmental Brain Research. 86. 101-113 (1995)
[文献書誌] K.Kobayashi, S. Morita, H. Sawada, T. Mizuguchi, K. Yamada, I. Nagatsu, K. Fujita, R.Kreitman, I. Pastan, T. Nagatsu.: "Immunotoxin-mediated conditional disruption of specific neurons in transgenic mice." Proc. Natl. Acad. Sci.USA. 92. 1132-1136 (1995)
[文献書誌] K.Kobayashi, S. Morita, H. Sawada, T. Mizuguchi, K. Yamada, I. Nagatsu, T. Hata, Y. Watanabe, K. Fujita, T. Nagatsu.: "Targeted disruption of the tyrosine hydroxylase locus results in severe catecholamine depletion and perinatal lethality in mice." J. Biochemistry Cytochemistry. 270(45). 27235-27243 (1995)
[文献書誌] K.Kobayashi, A. Ota, A. Togari, S. Morita, T. Mizuguchi, H. Sawada, K. Yamada, I. Nagatsu, S. Matsumoto, K. Fujita, T. Nagatsu.: "Alteration of catecholamine phenotype in transgenic mice influences expression of adrenergic receptor subtypes." J. Neurochemistry. 65(2). 429-501 (1995)
[文献書誌] K.Kosaka, Y.Aika, K. Toida, C. W. Heizmann, W. Hunzileer, M.Jacobowitz, I. Nagatsu, P. Streit, T. J. Visser, T. Kosaka.: "Chemically defined neuron groups and their subpopulations in the glomerular layer of the rat main olfactory bulb." Neuroscience Research. 23(1). 73-88 (1995)
[文献書誌] I. Nagatsu, H.Ichinose, M. Sakai, K. Titani, M. Suzuki, T. Nagatsu.: "Immunocytochemical localization of GTP cyclohydrolase I in the brain, adrenal gland, and liver of mice." J. Neural Transmission[General Section]. 102(3). 175-188 (1995)
[文献書誌] K. Sakai, N. Karasawa, K. Yamada, G. Isomura, I. Takagi, I. Nagatsu.: "Immunocytochemical Iocalization of APUD cells in the hypothalamus of the grass parakeet(Melopsittacus undulatus)and the lizard(Varanus exanthematicus)." Biogenic Amines. 11(1). 7-17 (1995)
[文献書誌] M. Sakai, T. Fujii, N. Karasawa, R. Arai, I. Nagatsu.: "Enhanced expression of tyrosine hydroxylase and aromatic L- amino acid decarboxylase in cedrebellar Purkinje cells of mouse after hyperosmotic stimuli." Neurosci. Lett.194. 142-144 (1995)
[文献書誌] S.Sawamura, M. Sawada, M. Ito, T. Nagatsu, I.Nagatsu, A. Suzumura, M. Shibuya, K. Sugita, T. Marunouchi.: "The bipotential glial progenitor cell line can develop into both oligodendrocyres and astrocytes in the mouse forebrain." Neurosci. Lett.188. 1-4 (1995)
[文献書誌] A. Seto- Ohshima, N. Karasawa, I. Nagatsu, K.Uchida, T. Isobe, S. Imai, S.Ozono, M. Onozuka.: "Nuclear localization of P70- like protein in neurons of the superior colliculus and substantia nigra of the gerbil." Acta Histochem. Cytochem.28(5). 461-463 (1995)
[文献書誌] C. Sumi- Ichinose, S. Hasegawa, H. Ichinose, H. Sawada, K. Kobayashi, M. Sakai, T. Fujii, H. Nomura, T. Nomura, I. Nagatsu, Y. Hagino, K. Fujita, T. Nagatsu.: "Alternative promoters that regulate tissue- specific expression of human aromatic L- amino acid decarboxylase." J. Neurochem.64. 514-524 (1995)
[文献書誌] M. Takayanagi, T. Watanabe, J. Yamada, I. Nagatsu.: "Immunocytochemical colocalizations of serotonin, aromatic L- amino acid decarboxylase and polypeptide hormones in A- and PP- cells of the ckicken endocrine pancreas." Tissue&Cell. 27(4). 439-446 (1995)
[文献書誌] K. Yamada, T. Takeuchi, N. Karasawa, M. Sakai, R. Arai, I. Nagatsu.: "Transgenic analysis of human tyrosine hydroxylase promoter using different reporter genes." Biogenic Amines. 11(4). 339-354 (1995)
[文献書誌] R. Arai, I. Nagatsu.: "Application of gold toning to immunogold- silver staining." In“Immunogold- silver Staining: Methods and Applications"(ed. Hayat, M. A.),CRC Press, Boca Raton, New York, London, Tokyo., 209-216 (1995)
[文献書誌] I. Nagatsu. N. Karasawa, K. Yamada, M. Sakai, T. Fujii, T. Takeuchi, T. Nagatsu.: "Expressionlof human tyrosine hydroxylase- chloramphenicol acetyltransferase(CAT)fusion gene in the brains of transgenic mice as examined by CAT immunocytochemistry." In “Alzheimer's and Parkinson's Diseases. Recent Developments", Hanin, I., Yoshida, M., Fisher, A. (eds.)Plenum Press, New York and London., 685-692 (1995)
[文献書誌] M. Ogawa, K. Ogura, Y. Nagatsuka, S. Ohta, H. Imai, I. Nagatsu, T. Nagatsu, M. Yoshida.: "Effect of chronic administration of 1,2,3,4,-tetrahydroisoquinoline and its derivatives on the monkey: immunohistochemical study." In“Alzheimer's and Parkinson's Diseases. Recent Developments", Hanin, I., Yoshida, M., Fisher, A. (eds.)Plenum Press, New York and London., 583-587 (1995)

1995 年度 実績報告書

ヒトカテコールアミン生合成酵素遺伝子導入トランスジェニックマウスの組織化学的解析

研究代表者

永津 郁子 藤田保健衛生大学, 医学部・解剖学, 教授 (80084573)

研究成果

[文献書誌] R. Arai, D. M. Jacobowitz, I. Nagatsu: "Up- tegulation of calretinin inthe supraoptic nucleus of the rat after chronic salt loading." Brain Res.673. 339-343 (1995)

[文献書誌] R. Arai, N. Karasawa, M. Geffard, I. Nagatsu.: " L- Dopa is converted to dopamine in serotonergic fibers of the striatum of the rat:a double- labeling immunofluorescence study." Neurosci. Lett.195. 195-198 (1995)

[文献書誌] R. Arai, N. Karasawa, T. Nagatsu, I. Nagatsu.: "Exogenous L-5-hydroxytryptophan is decarboxylated in neurons of the substantia nigra pars compacta and locus coeruleus of the rat." Brain Res.669. 145-149 (1995)

[文献書誌] R. Arai, K. Satoh, K. Kitahama, H. Ohshima, I. Nagatsu.: "Ultrastructural localization of nitric oxide synthase immunoreactivity in the frontal cortex of the monkey.21GC05:Biogenic Amines" 11(5). 409-415 (1995)

[文献書誌] N. Karasawa, R. Arai, G. Isomura, T. Nagatsu, I. Nagatsu.: "Chemical features of monoaminergic and non-monoaminergic neurons in the brain of laboratory shrew(Suncus murinus)are changed by systemic administration of monoamine precursors." Neuroscience Research. 24(1). 67-74 (1995)

[文献書誌] H. Kawano, K. Ohyama, K. Kawamura, I. Nagatsu.: "Migration of dopaminergic neurons in the embryonic mesencephalon of mice." Developmental Brain Research. 86. 101-113 (1995)

[文献書誌] K.Kobayashi, S. Morita, H. Sawada, T. Mizuguchi, K. Yamada, I. Nagatsu, K. Fujita, R.Kreitman, I. Pastan, T. Nagatsu.: "Immunotoxin-mediated conditional disruption of specific neurons in transgenic mice." Proc. Natl. Acad. Sci.USA. 92. 1132-1136 (1995)

[文献書誌] K.Kobayashi, A. Ota, A. Togari, S. Morita, T. Mizuguchi, H. Sawada, K. Yamada, I. Nagatsu, S. Matsumoto, K. Fujita, T. Nagatsu.: "Alteration of catecholamine phenotype in transgenic mice influences expression of adrenergic receptor subtypes." J. Neurochemistry. 65(2). 429-501 (1995)

[文献書誌] K.Kosaka, Y.Aika, K. Toida, C. W. Heizmann, W. Hunzileer, M.Jacobowitz, I. Nagatsu, P. Streit, T. J. Visser, T. Kosaka.: "Chemically defined neuron groups and their subpopulations in the glomerular layer of the rat main olfactory bulb." Neuroscience Research. 23(1). 73-88 (1995)

[文献書誌] I. Nagatsu, H.Ichinose, M. Sakai, K. Titani, M. Suzuki, T. Nagatsu.: "Immunocytochemical localization of GTP cyclohydrolase I in the brain, adrenal gland, and liver of mice." J. Neural Transmission[General Section]. 102(3). 175-188 (1995)

[文献書誌] K. Sakai, N. Karasawa, K. Yamada, G. Isomura, I. Takagi, I. Nagatsu.: "Immunocytochemical Iocalization of APUD cells in the hypothalamus of the grass parakeet(Melopsittacus undulatus)and the lizard(Varanus exanthematicus)." Biogenic Amines. 11(1). 7-17 (1995)

[文献書誌] M. Sakai, T. Fujii, N. Karasawa, R. Arai, I. Nagatsu.: "Enhanced expression of tyrosine hydroxylase and aromatic L- amino acid decarboxylase in cedrebellar Purkinje cells of mouse after hyperosmotic stimuli." Neurosci. Lett.194. 142-144 (1995)

[文献書誌] S.Sawamura, M. Sawada, M. Ito, T. Nagatsu, I.Nagatsu, A. Suzumura, M. Shibuya, K. Sugita, T. Marunouchi.: "The bipotential glial progenitor cell line can develop into both oligodendrocyres and astrocytes in the mouse forebrain." Neurosci. Lett.188. 1-4 (1995)

[文献書誌] A. Seto- Ohshima, N. Karasawa, I. Nagatsu, K.Uchida, T. Isobe, S. Imai, S.Ozono, M. Onozuka.: "Nuclear localization of P70- like protein in neurons of the superior colliculus and substantia nigra of the gerbil." Acta Histochem. Cytochem.28(5). 461-463 (1995)

[文献書誌] M. Takayanagi, T. Watanabe, J. Yamada, I. Nagatsu.: "Immunocytochemical colocalizations of serotonin, aromatic L- amino acid decarboxylase and polypeptide hormones in A- and PP- cells of the ckicken endocrine pancreas." Tissue&Cell. 27(4). 439-446 (1995)

[文献書誌] K. Yamada, T. Takeuchi, N. Karasawa, M. Sakai, R. Arai, I. Nagatsu.: "Transgenic analysis of human tyrosine hydroxylase promoter using different reporter genes." Biogenic Amines. 11(4). 339-354 (1995)

[文献書誌] R. Arai, I. Nagatsu.: "Application of gold toning to immunogold- silver staining." In“Immunogold- silver Staining: Methods and Applications"(ed. Hayat, M. A.),CRC Press, Boca Raton, New York, London, Tokyo., 209-216 (1995)

1995 年度実績報告書

永津郁子藤田保健衛生大学, 医学部・解剖学, 教授 (80084573)