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Persistent dermatoses and fetal abortion in HIV-1 Nef transgenic mice.


Int Conf AIDS. 1990 Jun 20-23;6(3):99 (abstract no. S.A.15). Unique

OBJECTIVE: To investigate the pathogenic role(s) of HIV-1 Nef using transgenic mouse models. METHODS and RESULTS: Three transgenic founder mice bearing integrated copies of a Nef expression plasmid linked to HIV-1 LTR were characterized by (i) a high incidence of fetal abortion associated with the transmission of the nef transgene and (ii) the appearance in adult animals of a persistent form of dermatosis marked by alopecia, papulosquamous lesions and acanthosis. Litters of Nef parents were abnormally small in number (one-half normal) due to the in utero death of both normal and transgenic fetuses. The number of fetal implants was normal. Fetal death occurred predominantly at 8 to 12 days into gestation, and at much later times as indicated by the high incidence of stillbirths (40% in one line). Stillbirths were essentially always transgenic. A significant proportion of surviving transgenic adults (1/3 in one line and 2/3 in another) developed, by six months of age and irregardless of sex, papulosquamous lesions typically restricted to the head and upper back. The primary histological finding was acanthosis and there was evidence of ulceration and lymphocytic infiltration in the dermis. The animal line with the severest and most penetrating form of dermatitis was analyzed for Nef protein and RNA expression. Expression at both levels was limited to the skin. CONCLUSIONS: Nef protein expression appears to functionally compromise normal skin differentiation. The cause of fetal death is probably due to Nef expression in early embryogenesis.

Abortion, Veterinary/COMPLICATIONS/*GENETICS/PATHOLOGY Animal Disease Models, Animal Female Fetal Death Gene Products, nef/BIOSYNTHESIS/*GENETICS HIV-1/*GENETICS Mice Mice, Transgenic Pregnancy RNA, Viral/ANALYSIS Skin Ulcer/COMPLICATIONS/GENETICS ABSTRACT


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