Spontaneous and inducible epidermal hyperplasia in transgenic mice expressing HIV-1 Nef.
The pathophysiological consequence of HIV-1 nef gene expression was investigated in transgenic mice carrying a cDNA for Nef linked to either the HIV-1 LTR or the MMTV LTR. In HIV/Nef transgenic mouse lines, nef expression was detected exclusively in the skin and a significant fraction of HIV/Nef transgenic animals (30-75%, depending on the line) spontaneously developed discrete proliferative skin lesions resembling papillomas that were often accompanied by a progressive ulceration of the epidermal cell layer. Nef protein was detected in the basal cell layer of the epidermis and was elevated in the proliferating epidermis. Epidermal cell proliferation could be induced by UV-C irradiation of HIV/Nef transgenic animals but not control mice. An increase in nef expression in the skin accompanied this proliferation. MMTV/Nef mouse lines expressed Nef RNA and protein in organs typically permissive for MMTV LTR-directed transcription but with no obvious pathological consequence.
Dickie
P
P
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Ramsdell
F
F
Notkins
A L
AL
Venkatesan
S
S
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D000078404:Epidermal Cells; D004817:Epidermis / Q000473:pathology / Q000528:radiation effects; D005260:Female; D005313:Fetal Death; D015870:Gene Expression; D015693:Gene Products, nef / Q000096:biosynthesis* / Q000235:genetics; D015754:Genes, nef; D016325:HIV Long Terminal Repeat; D006965:Hyperplasia; D008098:Litter Size; D008297:Male; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D012367:RNA, Viral / Q000032:analysis; D012091:Repetitive Sequences, Nucleic Acid; D012867:Skin / Q000166:cytology / Q000473:pathology* / Q000528:radiation effects; D014466:Ultraviolet Rays
D015693:Gene Products, nef; D012367:RNA, Viral