Two types of transgenic mouse systems were developed for investigations dealing with the in vivo expression of human immunodeficiency virus (HIV) gene products. The first utilized the HIV long terminal repeat linked to the bacterial gene, chloramphenicol acetyl transferase (CAT). The four transgenic strains obtained all exhibited spontaneous expression of CAT in the thymus, lens epithelium, spleen, heart, and the skin. Fractionation of ear skin from transgenic animals indicated that very high constitutive levels of CAT activity occurred in Langerhans cells. The latter are highly differentiated dendritic macrophages which comprise 2 - 5% of epidermal cells and actively produce virus in HIV positive individuals. Transgenic animals were also constructed which contain intact copies of the HIV proviral DNA. Progeny, resulting from the mating of one of the 5 founder animals to a non-transgenic mouse, develop an AIDS-like syndrome consisting of lymphadenopathy, a lung disease characterized by accumulation of lymphocytes around blood vessels, a psoriasis-like skin disease, retarded development, and death by day 28 of life. Non-transgenic littermates never develop the disease syndrome. HIV has been recovered from skin, lymph nodes and spleen. Immunologic studies indicate no depletion of the Leu 3/T4 subset of mouse T cells in the affected animals.
Showing the most recent 10 out of 14 publications
