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1996-02-26
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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).