TDAG51 Is Not Essential for Fas/CD95 Regulation and Apoptosis In Vivo

Abstract

Fas/CD95 is a key regulator of apoptotic signaling, which is crucial for the maintenance of homeostasis in peripheral lymphoid organs. TDAG51 has been shown to play critical roles in the up-regulation of Fas gene expression and T-cell apoptosis in vitro. In order to identify the role of TDAG51 in vivo, we generated TDAG51-deficient (TDAG51^−/−) mice. Northern blotting revealed no expression of TDAG51 in TDAG51^−/− mice, indicating that the TDAG51 gene was successfully targeted. TDAG51^−/− mice were healthy and showed no gross developmental abnormalities. While Fas-deficient mice display marked lymphadenopathy, splenomegaly, and lymphocytosis, TDAG51^−/− mice had no apparent defects in secondary lymphoid organs. Although TDAG51 is required for up-regulation of Fas expression in T-cell hybridomas, TDAG51^−/− mice expressed normal levels of Fas and had normal T-cell apoptosis. Therefore, we conclude that TDAG51 is not essential for Fas up-regulation and T-cell apoptosis in vivo. There are several known homologs of TDAG51, and these homologs may substitute for TDAG51 in TDAG51^−/−mice.

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TDAG51 Is Not Essential for Fas/CD95 Regulation and Apoptosis In Vivo

ACKNOWLEDGMENTS

S. Gong and N. Kim contributed equally to this work.

We thank C. G. Park and A. Santana for assistance with plasmid construction and mouse line maintenance, H. W. Lee and D. G. Kim for technical assistance with ES cell culture and flow cytometry, and Jennifer Macke for assistance preparing the text.

This work was supported in part by NIH grant (AI41082 to Y.C.).