Inactivation of Notch 1 in immature thymocytes does not perturb CD4 or CD8T cell development

Nat Immunol. 2001 Mar;2(3):235-41. doi: 10.1038/85294.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • CD4 Antigens / genetics
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Division
  • Cell Lineage
  • Cells, Cultured
  • Gene Deletion
  • Gene Targeting
  • Glucocorticoids / pharmacology
  • Integrases / genetics
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptor, Notch1
  • Receptors, Cell Surface*
  • Spleen / immunology
  • T-Lymphocyte Subsets / classification
  • Thymus Gland / cytology
  • Thymus Gland / immunology*
  • Transcription Factors*
  • Transgenes
  • Viral Proteins*

Substances

  • CD4 Antigens
  • Glucocorticoids
  • Membrane Proteins
  • Notch1 protein, mouse
  • Receptor, Notch1
  • Receptors, Cell Surface
  • Transcription Factors
  • Viral Proteins
  • Cre recombinase
  • Integrases