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1996-02-26
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Document 0404
DOCN M9620404
TI Neuronal expression of human immunodeficiency virus type 1 env proteins
in transgenic mice: distribution in the central nervous system and
pathological alterations.
DT 9602
AU Berrada F; Ma D; Michaud J; Doucet G; Giroux L; Kessous-Elbaz A;
Department of Pathology, Faculty of Medicine, University of; Montreal,
Quebec, Canada.
SO J Virol. 1995 Nov;69(11):6770-8. Unique Identifier : AIDSLINE
MED/96013771
AB It is now well documented that human immunodeficiency virus type 1
(HIV-1) induces encephalopathy in patients with AIDS. In vitro studies
have implicated the envelope protein (gp120) as a factor which causes
neuronal death. To better evaluate the role and elucidate the mechanisms
of gp120 neurotoxicity, we have developed transgenic mice carrying a
segment of the HIV-1 genome that expresses the viral gp160 protein under
the control of the human neurofilament light gene promoter. In two
separate lines of transgenic mice, the Env protein was found to be
expressed in several nuclei of the brain stem and in the anterior horns
of the spinal cord. The two lines showed identical patterns of Env
expression. Neuropathological evaluation revealed numerous abnormal
dendritic swellings in the immunostained motor neuron structures. Large
and numerous neuritic swellings were also prominent in the nucleus
gracilis and in the gracilis and cuneate fascicles. In addition,
reactive astrocytosis was observed in several immunoreactive areas of
the central nervous system. These transgenic mice offer a unique model
to further investigate the role of HIV-1 Env protein in neuronal
toxicity and to help elucidate the mechanisms that are involved.
DE Acquired Immunodeficiency Syndrome/*METABOLISM/PATHOLOGY Animal
Central Nervous System/METABOLISM/PATHOLOGY/*VIROLOGY Gene Expression
Gene Products, env/*BIOSYNTHESIS Genes, env Hela Cells Human HIV
Envelope Protein gp120/*BIOSYNTHESIS HIV-1/GENETICS/*METABOLISM Mice
Mice, Transgenic Neurofilament Proteins/GENETICS
Neurons/METABOLISM/PATHOLOGY/*VIROLOGY Promoter Regions (Genetics)
Restriction Mapping Spinal Cord/METABOLISM/PATHOLOGY/VIROLOGY Support,
Non-U.S. Gov't Transfection JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).