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 Resjournal_title
Journal of neuroscience researchauthors
Sawada H,Nishii K,Suzuki T,Hasegawa K,Hata T,Nagatsu I,Kreitman RJ,Pastan I,Nagatsu T,Kobayashi Kdoi
10.1002/(SICI)1097-4547(19980115)51:2<162::AID-JNRsubject
Has Abstractpub_date
1998-01-15 00:00:00pages
162-73issue
2eissn
0360-4012issn
1097-4547pii
10.1002/(SICI)1097-4547(19980115)51:2<162::AID-JNRjournal_volume
51pub_type
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