As part of an ongoing effort to create a transgenic, small-animal model of AIDS, researchers at TSI Corp. have producedtransgenic mice that express the human CD4 receptor (whichHIV targets) in a tissue-specific manner.
Reporting in the May issue of the journal Molecular andCellular Biology, Samuel Wadsworth and colleaguesdemonstrated that the expression of the human CD4 gene inmurine tissues was limited to the same cells -- primarilyperipheral blood mononuclear cells, as well as thymus andspleen -- as those that express the murine CD4 receptor.
Human CD4 protein, detected with an anti-human CD4monoclonal antibody, was present on the surface of roughly 50percent of the lymphocytes from all three of the transgenicmouse lines the researchers analyzed.
The mouse experiments were "proof in principle," but TSI ofWorcester, Mass., is actually interested in developing atransgenic rabbit as a small animal model for AIDS.
For instance, researcher Tom Kindt and colleagues at theNational Institute of Allergy and Infectious Diseases havealready demonstrated, in an upcoming issue of Proceedings ofthe National Academy of Sciences, that rabbit cell lines can beinfected by HIV, explained TSI's Wadsworth. (A Japanese grouphas published similar results.)
He added that Kindt's lab has also shown that rabbits can beinfected with HIV. "The goal of the work we're doing is toimprove the parameters of that infectious process," Wadsworthtold BioWorld.
"The most reliable aspects of disease in these animals relate toinfection of the spleen and brain, which have a long timecourse of development," he said. "We would like to see theanimal infected, look at the replication of the virus andmeasure the expression of viral gene products."
To that end, TSI (NASDAQ:TSIN) investigators have producedF1 (first-generation) transgenic rabbits that express the humanCD4 receptor in lymphocytes, spleen and thymus. The nextsteps will be to determine if the CD4-bearing rabbit cells can beinfected with HIV, as well as whether the human CD4 gene isheritable.
"Since the human CD4 transgene is appropriately regulated intransgenic mice, it is likely that appropriate CD4 regulation ...will be achieved in transgenic rabbits as well," according toWadsworth and his colleagues.
-- Jennifer Van Brunt Senior Editor
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