Inactivation of Notch 1 in immature thymocytes does not perturb CD4 or CD8T cell development.
Notch proteins influence cell-fate decisions in many developing systems. Several gain-of-function studies have suggested a critical role for Notch 1 signaling in CD4-CD8 lineage commitment, maturation and survival in the thymus. However, we show here that tissue-specific inactivation of the gene encoding Notch 1 in immature (CD25+CD44-)T cell precursors does not affect subsequent thymocyte development. Neither steady-state numbers nor the rate of production of CD4+ and CD8+ mature thymocytes is perturbed in the absence of Notch 1. In addition, Notch 1-deficient thymocytes are normally sensitive to spontaneous or glucocorticoid-induced apoptosis. In contrast to earlier reports, these data formally exclude an essential role for Notch 1 in CD4-CD8 lineage commitment, maturation or survival.
Ludwig Institute for Cancer Research, University of Lausanne, Epalinges, Switzerland.
A
A
Wolfer
T
T
Bakker
A
A
Wilson
M
M
Nicolas
V
V
Ioannidis
D R
DR
Littman
P P
PP
Lee
C B
CB
Wilson
W
W
Held
H R
HR
MacDonald
F
F
Radtke
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015704:CD4 Antigens / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002455:Cell Division; D019070:Cell Lineage; D002478:Cells, Cultured; D017353:Gene Deletion; D018390:Gene Targeting; D005938:Glucocorticoids / Q000494:pharmacology; D019426:Integrases / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000145:classification; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*; D014157:Transcription Factors; D019076:Transgenes; D014764:Viral Proteins
D015704:CD4 Antigens; D005938:Glucocorticoids; D008565:Membrane Proteins; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases