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

Dianne Langford, Byung Oh Kim, Wei Zou, Yan Fan, Pejman Rahimain, Ying Liu, Johnny J. He

Research output: Contribution to journalReview article

12 Scopus citations

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/mlandledto 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.

Original languageEnglish
Pages (from-to)168-179
Number of pages12
JournalJournal of NeuroVirology
Volume24
Issue number2
DOIs
StatePublished - 15 Nov 2018

Keywords

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

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