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

Abstract:

: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 alpha subunit under the control of the dopamine beta-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.

journal_name

J Neurosci Res

authors

Sawada H,Nishii K,Suzuki T,Hasegawa K,Hata T,Nagatsu I,Kreitman RJ,Pastan I,Nagatsu T,Kobayashi K

doi

10.1002/(SICI)1097-4547(19980115)51:2<162::AID-JNR

subject

Has Abstract

pub_date

1998-01-15 00:00:00

pages

162-73

issue

2

eissn

0360-4012

issn

1097-4547

pii

10.1002/(SICI)1097-4547(19980115)51:2<162::AID-JNR

journal_volume

51

pub_type

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