By using DDRT-PCR and EST segment ligation, a novel mouse thymus involution related gene Rwdd1 was identified. The reading frame encoded a protein of 243 amino acid residues which contained an RWD domain at the N terminus. Rwdd1 expression in thymus was decreased in aged and oxidatively stressed mice. It was found to be expressed extensively in thymocytes and thymic epithelial cells. The expression level of Rwdd1 could affect the transactivation activity of androgen receptor (AR) in transiently transfected thymic epithelial cells. However, no direct interaction could be detected by fluorescence resonance energy transfer (FRET) analysis. In conclusion, Rwdd1 is a thymus involution related protein that may indirectly affect AR signaling pathway.