Document 0250
 DOCN  M95A0250
 TI    Transgenic models of HIV-1 [editorial]
 DT    9510
 AU    Klotman PE; Rappaport J; Ray P; Kopp JB; Franks R; Bruggeman LA; Notkins
       AL
 SO    AIDS. 1995 Apr;9(4):313-24. Unique Identifier : AIDSLINE MED/95314785
 AB    Transgenic technology has been very successful at providing insights
       into possible processes involved in HIV-induced pathogenesis. The
       availability of these small animal models for the study of HIV-related
       syndromes including KS, epidermal proliferative lesions, HIV-associated
       nephropathy, AIDS-related growth failure and cachexia may well
       facilitate the development of novel therapies for these complications.
       Other phenotypes created in mice, such as cataracts and hepatic cancer
       [59], may not have human analogies but may still provide insight into
       pathogenesis. Thus, transgenic models have already provided resources to
       study many manifestations of AIDS and others are likely to be developed.
       The optimal strategy for designing future transgenic animals, however,
       is less clear. No transgenic mouse model has been generated to date that
       will provide an avenue for vaccine development. This advance awaits the
       further discovery of the host factors that facilitate the virus
       replicative cycle in humans and a better understanding of these pathways
       in the mouse. For the development of molecular-based therapy, however,
       the currently available models may well be adequate to test molecular
       inhibitors of transcription [7,60,61] and post-transcriptional
       processing of viral mRNA [62]. Whether single or multigenic constructs
       under the control of the LTR are better or worse for this purpose is a
       debatable issue. Transgenic technology may yet make an additional
       contribution to the development of molecular therapy for AIDS. The best
       method of demonstrating that a gene therapeutic strategy is safe to
       administer to patients has not been determined. By introducing
       potentially therapeutic constructs into mice as transgenes, their safety
       can be assessed in many different cell types in vivo, analogous to
       toxicological testing in rodents for systemically administered drugs.
       Thus, transgenic technology has already provided insights into the
       pathogenesis of HIV-1. While it has not yet proven its utility for
       vaccine development, transgenic technology holds the promise of being an
       active participant in the development of both safe and effective gene
       therapy approaches for the treatment of AIDS.
 DE    Animal  AIDS Dementia Complex/ETIOLOGY  AIDS-Associated
       Nephropathy/ETIOLOGY  Cachexia/ETIOLOGY  Cataract/ETIOLOGY  CD4-Positive
       T-Lymphocytes  Disease Models, Animal  Human  HIV
       Infections/COMPLICATIONS/*ETIOLOGY  *HIV-1/GENETICS/PATHOGENICITY  Mice
       Mice, Transgenic  Sarcoma, Kaposi's/ETIOLOGY  Skin
       Diseases/ETIOLOGY/PATHOLOGY  EDITORIAL  REVIEW  REVIEW, TUTORIAL
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).