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Transgenic mice expressing HIV-1 envelope protein gp120 in the brain as an animal model in neuroAIDS research
Authors:Victoria E. Thaney  Ana B. Sanchez  Jerel A. Fields  Arpi Minassian  Jared W. Young  Ricky Maung  Marcus Kaul
Affiliation:1.Infectious and Inflammatory Disease Center,Sanford Burnham Prebys Medical Discovery Institute,La Jolla,USA;2.Department of Psychiatry,University of California, San Diego,La Jolla,USA;3.Division of Biomedical Sciences, School of Medicine,University of California, Riverside,Riverside,USA
Abstract:
HIV-1 infection causes injury to the central nervous system (CNS) and is often associated with neurocognitive disorders. One model for brain damage seen in AIDS patients is the transgenic (tg) mouse expressing a soluble envelope protein gp120 of HIV-1 LAV in the brain in astrocytes under the control of the promoter of glial fibrillary acidic protein. These GFAP-gp120tg mice manifest several key neuropathological features observed in AIDS brains, such as decreased synaptic and dendritic density, increased numbers of activated microglia, and pronounced astrocytosis. Several recent studies show that brains of GFAP-gp120tg mice and neurocognitively impaired HIV patients share also a significant number of differentially regulated genes, activation of innate immunity and other cellular signaling pathways, disturbed neurogenesis, and learning deficits. These findings support the continued relevance of the GFAP-gp120tg mouse as a useful model to investigate neurodegenerative mechanisms and develop therapeutic strategies to mitigate the consequences associated with HIV infection of the CNS, neuroAIDS, and HAND.
Keywords:
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