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

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)162-173
Number of pages12
JournalJournal of Neuroscience Research
Issue number2
Publication statusPublished - 15-01-1998

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience


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