Tat-induced lesions in transgenic mice do not correlate with the HIV-1 LTR transactivation.
The product of the tat gene is the most potent transcriptional trans-activator of the HIV-1 LTR (Human Immunodeficiency Virus type 1 Long Terminal Repeat) and might be predicted to be one of the HIV-1 proteins involved in the pathogenesis of AIDS-associated tumors. Deciphering its role in vivo may imply generation of transgenic mouse models displaying different spectra of tat expression. However, it remains difficult to correlate the mRNA expression, the protein production and the eventual pathological consequences in the animal. Our goal in this work was to elaborate a binary transgenic system allowing such an approach, the correlation of the transgene expression in different tissues and the production of the Tat protein, tested as a trans-activator in vivo, with its pathogenic effects. No direct linkage was evident between the degree of transactivation and pathogenesis. Indeed, only benign lesions were observed in malpighian epithelia, where the production of the Tat protein was clearly evidenced by its transactivating property.
Fergelot
P
P
Laboratoire de génétique et pathologie expérimentales, INSERM U 380, Institut Cochin de génétique moléculaire, Paris, France.
Molina
T
T
Blanchet
P
P
Grimber
G
G
Duquenne
O
O
Couton
D
D
Zider
A
A
Briand
P
P
Cavard
C
C
D000818:Animals; D004848:Epithelium / Q000293:injuries; D015696:Gene Products, tat / Q000235:genetics* / Q000378:metabolism; D015756:Genes, tat / Q000235:genetics; D015497:HIV-1 / Q000235:genetics*; D008317:Malpighian Tubules / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic; D015533:Transcriptional Activation; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus