Autonomic neuropathy in transgenic mice caused by immunotoxin targeting of the peripheral nervous system

Hirohide Sawada, Kazuhiro Nishii, Tatsuyo Suzuki, Kayo Hasegawa, Tadayoshi Hata, Ikuko Nagatsu, Robert J. Kreitman, Ira Pastan, Toshiharu Nagatsu, Kazuto Kobayashi

研究成果: Article

10 引用 (Scopus)

抄録

Autonomic neuropathy in several neurodegenerative disorders results from disturbance in physiological functions of different cell types in the central and peripheral nervous systems. For a clearer understanding of the etiology and pathogenesis of the autonomic disorders it is necessary to create animal models in which degeneration of the causative neuronal types can be induced. Immunotoxin-mediated cell targeting (IMCT) is a novel transgenic mouse technology for eliminating selective cell types with the cytotoxic activity of a recombinant immunotoxin anti-Tac(Fv)-PE40. In this study we conditionally disrupted peripheral catecholaminergic cells with IMCT to generate a mouse model developing autonomic failure based on primary defects of the sympathetic nervous system. Transgenic mice expressing human interleukin-2 receptor α subunit under the control of the dopamine β- hydroxylase gene promoter were intravenously treated with a proper dose of anti-Tac(Fv)-PE40. The immunotoxin induced a selective loss of the target cells in peripheral tissues of the transgenic mice and an impairment of catecholamine metabolism in the tissues. Targeting of the peripheral catecholaminergic cells resulted in severe and progressive phenotypic abnormalities mainly characterized by cardiac dysfunction, hypoactivity, and hypothermia, which explain development of autonomic neuropathy. Our IMCT strategy is useful for elucidating the involvement of different neuronal types and their interactions in the development and symptom of autonomic disorders.

元の言語English
ページ(範囲)162-173
ページ数12
ジャーナルJournal of Neuroscience Research
51
発行部数2
DOI
出版物ステータスPublished - 15-01-1998

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Immunotoxins
Peripheral Nervous System
Transgenic Mice
Interleukin-2 Receptors
Sympathetic Nervous System
Mixed Function Oxygenases
Hypothermia
Neurodegenerative Diseases
Catecholamines
Dopamine
Central Nervous System
Animal Models
Technology

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

これを引用

Sawada, Hirohide ; Nishii, Kazuhiro ; Suzuki, Tatsuyo ; Hasegawa, Kayo ; Hata, Tadayoshi ; Nagatsu, Ikuko ; Kreitman, Robert J. ; Pastan, Ira ; Nagatsu, Toshiharu ; Kobayashi, Kazuto. / Autonomic neuropathy in transgenic mice caused by immunotoxin targeting of the peripheral nervous system. :: Journal of Neuroscience Research. 1998 ; 巻 51, 番号 2. pp. 162-173.
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Sawada, H, Nishii, K, Suzuki, T, Hasegawa, K, Hata, T, Nagatsu, I, Kreitman, RJ, Pastan, I, Nagatsu, T & Kobayashi, K 1998, 'Autonomic neuropathy in transgenic mice caused by immunotoxin targeting of the peripheral nervous system', Journal of Neuroscience Research, 巻. 51, 番号 2, pp. 162-173. https://doi.org/10.1002/(SICI)1097-4547(19980115)51:2<162::AID-JNR5>3.0.CO;2-B

Autonomic neuropathy in transgenic mice caused by immunotoxin targeting of the peripheral nervous system. / Sawada, Hirohide; Nishii, Kazuhiro; Suzuki, Tatsuyo; Hasegawa, Kayo; Hata, Tadayoshi; Nagatsu, Ikuko; Kreitman, Robert J.; Pastan, Ira; Nagatsu, Toshiharu; Kobayashi, Kazuto.

:: Journal of Neuroscience Research, 巻 51, 番号 2, 15.01.1998, p. 162-173.

研究成果: Article

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AU - Sawada, Hirohide

AU - Nishii, Kazuhiro

AU - Suzuki, Tatsuyo

AU - Hasegawa, Kayo

AU - Hata, Tadayoshi

AU - Nagatsu, Ikuko

AU - Kreitman, Robert J.

AU - Pastan, Ira

AU - Nagatsu, Toshiharu

AU - Kobayashi, Kazuto

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N2 - Autonomic neuropathy in several neurodegenerative disorders results from disturbance in physiological functions of different cell types in the central and peripheral nervous systems. For a clearer understanding of the etiology and pathogenesis of the autonomic disorders it is necessary to create animal models in which degeneration of the causative neuronal types can be induced. Immunotoxin-mediated cell targeting (IMCT) is a novel transgenic mouse technology for eliminating selective cell types with the cytotoxic activity of a recombinant immunotoxin anti-Tac(Fv)-PE40. In this study we conditionally disrupted peripheral catecholaminergic cells with IMCT to generate a mouse model developing autonomic failure based on primary defects of the sympathetic nervous system. Transgenic mice expressing human interleukin-2 receptor α subunit under the control of the dopamine β- hydroxylase gene promoter were intravenously treated with a proper dose of anti-Tac(Fv)-PE40. The immunotoxin induced a selective loss of the target cells in peripheral tissues of the transgenic mice and an impairment of catecholamine metabolism in the tissues. Targeting of the peripheral catecholaminergic cells resulted in severe and progressive phenotypic abnormalities mainly characterized by cardiac dysfunction, hypoactivity, and hypothermia, which explain development of autonomic neuropathy. Our IMCT strategy is useful for elucidating the involvement of different neuronal types and their interactions in the development and symptom of autonomic disorders.

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