T cells develop normally in the absence of both Deltex1 and Deltex2

Deltex1, Deltex2, and Deltex4 form a family of related proteins that are the mammalian homologues of Drosophild Deltex, a known regulator of Notch signals. Deltext is highly induced by Notch signaling in thymocytes, and overexpression of Deltexl in T-cell progenitors can block Notch signals, suggesting that Deltexl may play an important role in regulating Notch signals during T-cell development. A recent report found that T cells develop normally in mice carrying a targeted deletion in the Deltexl gene (S. Storck, F. Delbos, N. Stadler, C. Thirion-Delallande, F. Bernex, C. Verthuy, P. Ferrier, J. C. Weill, and C. A. Reynaud, Mol. Cell. Biol. 25: 1437-1445, 2005), suggesting that other Deltex homologues may compensate in Deltexldeficient T cells. We generated mice that lack expression of both Deltexl and De1tex2 by gene targeting and further reduced expression of Deltex4 in Deltexl/Deltex2 double-deficient T-cell progenitors using RNA interference. Using a sensitive in vitro assay, we found that Notch signaling is more potent in cells expressing lower levels of Deltex proteins. Nevertheless, we were unable to detect any significant defects in thymocyte maturation in Deltexl/Deltex2 double-knockout mice. Together these data suggest that Deltex can act as a negative regulator of Notch signals in T cells but that endogenous levels of Deltexl and De1tex2 are not important for regulating Notch signals during thymocyte development.