Document 0799
 DOCN  M9460799
 TI    Severe immunodeficiency associated with a human immunodeficiency virus 1
       NEF/3'-long terminal repeat transgene.
 DT    9404
 AU    Lindemann D; Wilhelm R; Renard P; Althage A; Zinkernagel R; Mous J;
       Department of Biology, F. Hoffmann-La Roche Ltd., Basel,; Switzerland.
 SO    J Exp Med. 1994 Mar 1;179(3):797-807. Unique Identifier : AIDSLINE
       MED/94157400
 AB    We have generated several transgenic mouse strains carrying a human
       immunodeficiency virus 1 (HIV-1) NEF/3' long terminal repeat (LTR)
       transgene under control of a T cell-specific promoter-enhancer element,
       showing a depletion of CD4+ T cells in the thymus and periphery. The
       immunological functions of the line with the most dramatic changes in
       lymphocyte populations, B6/338L, were analyzed in greater detail. The
       presence of the transgene in the heterozygous animal is associated with
       a dominant severe immunodeficiency. Older animals develop
       lymph-adenopathy and splenomegaly. CD4+CD8+ and CD4+CD8- single positive
       thymocytes already are depleted in these mice at the earliest stages in
       ontogeny, and peripheral T cells are reduced in frequency and present
       cell surface marker expression, which is characteristic for memory and
       activated T cells. The immunological response of B6/338L mice to several
       viral infections is also greatly impaired. Thus, the HIV-1 NEF/3' LTR as
       transgene in T cells can cause immunodeficiency and disease with
       striking similarities to a known retrovirus-induced immunodeficiency
       called murine AIDS (H. C. Morse III, S. K. Chattopadhyay, M. Makino, T.
       N. Frederickson, A. W. Hugin, and J. W. Hartley. 1992. AIDS. 6:607).
 DE    Aging/IMMUNOLOGY  Animal  Antibody Formation  Antigens,
       CD4/ANALYSIS/IMMUNOLOGY  Antigens, CD8/ANALYSIS/IMMUNOLOGY  Base
       Sequence  DNA Primers  Female  Fetal Development/IMMUNOLOGY  Flow
       Cytometry  *Genes, nef  Heterozygote Detection  *HIV Long Terminal
       Repeat  HIV-1/*GENETICS  Immunologic Deficiency
       Syndromes/*GENETICS/*IMMUNOLOGY  Lymphocyte Depletion  Male  Mice  Mice,
       Inbred C57BL  Mice, Inbred DBA  Mice, Inbred Strains  Mice, Transgenic
       Molecular Sequence Data  Murine Acquired Immunodeficiency
       Syndrome/*IMMUNOLOGY  Organ Specificity  Polymerase Chain Reaction
       Support, Non-U.S. Gov't  T-Lymphocyte Subsets/IMMUNOLOGY
       T-Lymphocytes/*IMMUNOLOGY  JOURNAL ARTICLE

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