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Normal immune development and glucocorticoid-induced thymocyte apoptosis in mice deficient for the T-cell

Caius G Radu1, Donghui Cheng, Amar Nijagal

  • 1Department of Microbiology, Immunology and Molecular Genetics, University of California--Los Angeles, Los Angeles, California 90095-1662, USA.

Molecular and Cellular Biology
|December 31, 2005
PubMed

Insights

T-cell death-associated gene 8 (TDAG8) is not critical for immune development or glucocorticoid-induced apoptosis, despite its dynamic expression during thymocyte maturation. TDAG8 knockout mice showed normal immune functions and responses.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • T-cell death-associated gene 8 (TDAG8) is a G-protein-coupled receptor upregulated by glucocorticoids (GCs).
  • Overexpression studies suggested TDAG8 involvement in psychosine-mediated cytokinesis inhibition and GC-induced apoptosis.
  • The physiological role of TDAG8 in immune development remained unclear.

Purpose of the Study:

  • To investigate the physiological function of TDAG8 in immune development.
  • To determine TDAG8's role in psychosine-mediated cytokinesis inhibition and GC-induced apoptosis.
  • To generate and characterize TDAG8 knockout (KO) mice with an enhanced green fluorescent protein (eGFP) reporter.

Main Methods:

  • Homologous recombination was used to generate TDAG8 KO mice.
  • An eGFP reporter was inserted into the tdag8 locus to visualize TDAG8 expression.
  • Thymocyte development, selection, immune functions, psychosine-induced cell effects, and GC-induced apoptosis were analyzed in KO mice.

Main Results:

  • TDAG8 expression exhibited dynamic regulation during thymocyte development, mirroring known apoptosis modulators.
  • TDAG8 KO mice displayed normal thymocyte maturation, selection, and major immune functions.
  • TDAG8 was dispensable for psychosine-induced multinucleation and GC-induced thymocyte apoptosis.

Conclusions:

  • TDAG8 does not play a critical role in T-lymphocyte development, immune function, or GC-induced cell death.
  • TDAG8 is not essential for psychosine-mediated inhibition of cytokinesis.
  • The generated TDAG8-eGFP reporter mouse strain is a valuable tool for studying T-lymphocyte maturation.

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