       Document 0236
 DOCN  M9620236
 TI    Transgenic mice carrying the diphtheria toxin A chain gene under the
       control of the granzyme A promoter: expected depletion of cytotoxic
       cells and unexpected depletion of CD8 T cells.
 DT    9602
 AU    Aguila HL; Hershberger RJ; Weissman IL; Department of Pathology,
       Stanford University Medical Center, CA; 94305, USA.
 SO    Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10192-6. Unique Identifier
       : AIDSLINE MED/96036050
 AB    We have generated transgenic mice bearing the diphtheria toxin A chain
       (DTA) gene under the control of granzyme A (GrA) promoter sequences
       (GrA-DTA). GrA is expressed in activated cytotoxic cells but not in
       their immediate progenitors. These GrA-DTA mice are deficient in
       cytotoxic functions, indicating that most cytotoxic cells express GrA in
       vivo. Surprisingly, one founder strain containing a multicopy GrA-DTA
       insert show a marked and selective deficiency in CD8+ cells in
       peripheral lymphoid organs. This depletion was not observed in thymus,
       where the distribution of CD4+ and CD8+ cells is normal. Moreover, the
       emigration of T cells from thymus is normal, indicating that the
       depletion occurs in the periphery. GrA-DTA mice should be useful as
       models to dissect the role of cytotoxic cells in immune responses and as
       recipients of normal and neoplastic hematopoietic cells. The selective
       depletion of CD8+ cells in one founder strain could have implications
       for postthymic T-cell development.
 DE    Animal  *Cytotoxicity, Immunologic  CD4-Positive
       T-Lymphocytes/IMMUNOLOGY  CD8-Positive T-Lymphocytes/*IMMUNOLOGY
       Diphtheria Toxin/BIOSYNTHESIS/*GENETICS  Female  *Lymphocyte Depletion
       Male  Mice  Mice, Inbred BALB C  Mice, Inbred C3H  Mice, Inbred C57BL
       Mice, Transgenic  Peptide Fragments/BIOSYNTHESIS/*GENETICS  Polymerase
       Chain Reaction  *Promoter Regions (Genetics)  Restriction Mapping
       Serine Proteinases/*GENETICS  Support, Non-U.S. Gov't  Support, U.S.
       Gov't, P.H.S.  T-Lymphocytes/*IMMUNOLOGY  Thymus Gland/IMMUNOLOGY
       JOURNAL ARTICLE

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

