TDAG51 is not essential for Fas/CD95 regulation and apoptosis in vivo.
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.
Rho
J
J
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 421 Curie Blvd., Philadelphia, PA 19104, USA.
Gong
S
S
Kim
N
N
Choi
Y
Y
D000818:Animals; D017209:Apoptosis; D015152:Blotting, Northern; D002455:Cell Division; D003208:Concanavalin A / Q000494:pharmacology; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology*; D015854:Up-Regulation; D019014:fas Receptor / Q000378:metabolism*
D018076:DNA, Complementary; D008070:Lipopolysaccharides; C114072:Phlda1 protein, mouse; D014157:Transcription Factors; D019014:fas Receptor; D003208:Concanavalin A