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J Neurovirol. 2018 Apr;24(2):168-179. doi: 10.1007/s13365-017-0598-9. Epub 2017 Nov 15.

Doxycycline-inducible and astrocyte-specific HIV-1 Tat transgenic mice (iTat) as an HIV/neuroAIDS model.

Author information

1
Department of Neuroscience, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USA.
2
School of Food Science & Biotechnology and College of Agriculture & Life Sciences, Kyungpook National University, Daegu, 702-701, South Korea.
3
The 1st Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China.
4
Graduate School of Biomedical Sciences, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX, 76107, USA.
5
Graduate School of Biomedical Sciences, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX, 76107, USA. johnny.he@unthsc.edu.

Abstract

HIV-1 Tat is known to be neurotoxic and important for HIV/neuroAIDS pathogenesis. However, the overwhelming majority of the studies involved use of recombinant Tat protein. To understand the contributions of Tat protein to HIV/neuroAIDS and the underlying molecular mechanisms of HIV-1 Tat neurotoxicity in the context of a whole organism and independently of HIV-1 infection, a doxycycline-inducible astrocyte-specific HIV-1 Tat transgenic mouse (iTat) was created. Tat expression in the brains of iTat mice was determined to be in the range of 1-5 ng/ml and led to astrocytosis, loss of neuronal dendrites, and neuroinflammation. iTat mice have allowed us to define the direct effects of Tat on astrocytes and the molecular mechanisms of Tat-induced GFAP expression/astrocytosis, astrocyte-mediated Tat neurotoxicity, Tat-impaired neurogenesis, Tat-induced loss of neuronal integrity, and exosome-associated Tat release and uptake. In this review, we will provide an overview about the creation and characterization of this model and its utilities for our understanding of Tat neurotoxicity and the underlying molecular mechanisms.

KEYWORDS:

Brain; HIV-1; Mouse model; Tat; Transgenic

PMID:
29143286
PMCID:
PMC6444363
DOI:
10.1007/s13365-017-0598-9
[Indexed for MEDLINE]
Free PMC Article

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