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.
- URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11224523
Keywords: Animals ; Antigens ; CD4/genetics ; Apoptosis/drug effects ; CD4-Positive T-Lymphocytes/drug effects/*immunology ; CD8-Positive T-Lymphocytes/drug effects/*immunology ; Cell Division ; Cell Lineage ; Cells ; Cultured ; Gene Deletion ; Gene Targeting ; Glucocorticoids/pharmacology ; Integrases/genetics ; Membrane Proteins/genetics/*physiology ; Mice ; Mice ; Inbred C57BL ; Mice ; Knockout ; Receptor ; Notch1 ; *Receptors ; Cell Surface ; Research Support ; Non-U.S. Gov't ; Spleen/immunology ; T-Lymphocyte Subsets/classification ; Thymus Gland/cytology/*immunology ; *Transcription Factors ; Transgenes ; *Viral Proteins
Ludwig Institute for Cancer Research, University of Lausanne, Epalinges, Switzerland.
Record created on 2006-12-05, modified on 2016-08-08