title: A transgenic model of transactivation by the Tax protein of HTLV-I.
abstract: The human T-lymphotropic virus type I (HTLV-I) Tax protein is a transcriptional regulatory protein that has been suggested to play a causal role in the development of several HTLV-I-associated diseases. Tax regulates expression of its own LTR and of certain cellular promoters perhaps by usurping the function of the host transcriptional machinery. We have established a transgenic mouse model system to define the spectrum of tissues in vivo that are capable of supporting Tax-mediated transcriptional transactivation. Transgenic mice carrying the HTLV-I LTR driving expression of the Escherichia coli beta-galactosidase (beta gal) gene were generated, and this LTR-beta gal gene was transcriptionally inactive in all tissues. When LTR-beta gal mice were mated to transgenic mice carrying the same LTR driving expression of the HTLV-I tax gene, mice that carried both transgenes showed restricted expression of the beta gal reporter gene in several tissues including muscle, bone, salivary glands, skin, and nerve. In addition, a dramatic increase in the number of beta gal-expressing cells was seen in response to wounding. These observations provide direct evidence for viral transactivation in vivo, delimit the tissues capable of supporting that transactivation, and provide a model system to study the mechanism of gene regulation by Tax.
authors.affiliation: Jerome H. Holland Laboratory, American Red Cross, Rockville, Maryland 20855.
authors.forename: C J
authors.initials: CJ
authors.lastname: Bieberich
authors.forename: C M
authors.initials: CM
authors.lastname: King
authors.forename: B T
authors.initials: BT
authors.lastname: Tinkle
authors.forename: G
authors.initials: G
authors.lastname: Jay
mesh_terms: D000818:Animals; D015139:Blotting, Southern; D016356:Gene Products, tax / Q000235:genetics*; D016355:Genes, pX; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D015533:Transcriptional Activation; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D016356:Gene Products, tax; D001616:beta-Galactosidase