A novel transgenic mouse model for the in vivo evaluation of anti-human immunodeficiency virus type 1 drugs.
We have developed a binary transgenic mouse system that allows easy in vivo evaluation of new anti-human immunodeficiency virus type 1 (HIV-1) drugs or therapies specifically designed to target the viral transactivator protein (TAT) or long terminal repeat (LTR) functions. This approach consists of a simple genetic cross between an "activator" transgenic mouse expressing the HIV-1-tat gene exclusively to T lymphocytes and a "target" transgenic mouse bearing a silent reporter gene whose expression is under the control of the HIV-1-LTR. As expected, most of the target transgenic animals did not express the reporter gene; on the contrary, all the double-transgenic mice bearing both the activator and target transgenes strongly expressed the TAT-induced reporter gene. The choice of a secreted human alpha 1-antitrypsin variant (alpha 1-AT) as reporter gene readily permits in a single animal the quantitative determination of the plasma level of alpha 1-AT protein before and after anti-LTR or anti-TAT treatments. Such mice may be valuable as new laboratory models for the in vivo evaluation of agents with potential anti-HIV-1 activity.
Mehtali
M
M
TRANSGENE S.A., Strasbourg, France.
Munschy
M
M
Ali-Hadji
D
D
Kieny
M P
MP
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D015756:Genes, tat / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy; D016325:HIV Long Terminal Repeat / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D015533:Transcriptional Activation; D000515:alpha 1-Antitrypsin / Q000235:genetics
D000998:Antiviral Agents; D000515:alpha 1-Antitrypsin