Morphological, histochemical, immunohistochemical, and ultrastructural characterization of tumors and dysplastic and non-neoplastic lesions arising in BK virus/tat transgenic mice

To study the role in AIDS pathogenesis of the human immunodeficiency virus type 1 (HIV-1) Tat protein, a transactivator of viral and cellular genes, w e generated transgenic mice with a recombinant DNA containing BK virus (BKV ) early region and the HIV-1 tat gene, directed by its own promoter-enhance r. DNA hybridization revealed that the transgene is stably maintained in al l organs of transgenic mice as a tandem insertion in a number of copies ran ging from 5 to 20 per cell. In addition, tat and BKV RNA were expressed in all tissues. Transgenic mice developed three types of lesions: 1) tumors, 2 ) hyperplastic and dysplastic lesions, and 3) non-neoplastic lesions. Tumor s of different histotypes, such as lymphomas, adenocarcinomas of skin gland s, leiomyosarcomas, skin squamous cell carcinomas, hepatomas, hepato carcin omas, and cavernous Liver hemangiomas, developed in 29% of transgenic anima ls. The majority of tumors were malignant, invasive, and producing metastas es, Conversely, tumors of only two histotypes (lymphomas and adenocarcinoma s of skin glands) appeared in control mice. Hyperplastic and dysplastic les ions were more frequent in transgenic than in control mice and involved the skin or its adnexes, the liver and the rectum, indicating multiple targets for the activity of the transgene, Pyelonephritis, frequently complicated with hydronephrosis, inflammatory eye lesions, and amyloid depositions repr esented the most frequent non-neoplastic lesions detected in transgenic mic e. Many of the pathological findings observed in this animal model are comp arable to similar lesions appearing in AIDS patients, suggesting a relevant role for Tat in the pathogenesis of such lesions during the course of AIDS .