Document 0143
 DOCN  M94A0143
 TI    Modeling human lymphoid precursor cell gene therapy in the SCID-hu
       mouse.
 DT    9412
 AU    Akkina RK; Rosenblatt JD; Campbell AG; Chen IS; Zack JA; Department of
       Medicine, UCLA School of Medicine 90024-1678.
 SO    Blood. 1994 Sep 1;84(5):1393-8. Unique Identifier : AIDSLINE
       MED/94348058
 AB    Gene therapy of human T-lymphocyte disorders, including acquired
       immunodeficiency syndrome (AIDS), would be greatly facilitated by the
       development of an in vivo system in which transduced human hematopoietic
       stem cells can be used to reconstitute the T-lymphoid compartment. Here
       we use the SCID-hu mouse as a recipient for human CD34+ hematopoietic
       progenitor cells transduced in vitro with a retroviral vector carrying
       the neomycin resistance gene (neoR). The transduced cells engraft and
       reconstitute the lymphoid compartments of the human thymus implant with
       as few as 5 x 10(4) CD34+ cells. The neoR gene was expressed at low
       levels in human thymocytes and there was no apparent effect on thymocyte
       differentiation as a result of vector transduction. Thus, this SCID-hu
       mouse system is the first in vivo model showing human thymopoiesis after
       transduction of exogenous vectors, and should allow preclinical testing
       of gene therapeutic reagents designed to function in human cells of the
       T-lymphoid lineage. Because human immunodeficiency virus type 1
       infection induces depletion of human thymocytes in SCID-hu mice, this
       system may be particularly valuable in evaluating efficacy of gene
       therapies to combat AIDS.
 DE    Acquired Immunodeficiency Syndrome/THERAPY  Animal  Antigens,
       CD/ANALYSIS/*BIOSYNTHESIS  Base Sequence  Disease Models, Animal  Drug
       Resistance, Microbial/*GENETICS  DNA Primers  Fetal Tissue
       Transplantation  Gene Therapy/*METHODS  Hematopoietic Stem
       Cells/*TRANSPLANTATION  Human  *Lymphocyte Transfusion  Mice  Mice, SCID
       Molecular Sequence Data  Phosphotransferases (Alcohol Group
       Acceptor)/BIOSYNTHESIS/  GENETICS  Polymerase Chain Reaction  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  T-Lymphocytes  JOURNAL
       ARTICLE

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