Gadd45γ Is Dispensable for Normal Mouse Development and T-Cell Proliferation

Gadd45γ, a family member of the growth arrest and DNA damage-inducible gene family 45 (Gadd45), is strongly induced by interleukin-2 (IL-2) in peripheral T cells. While in most tissues all Gadd45 family members are expressed, Gadd45γ is the only member that is induced by IL-2. Here we show that the IL-2-induced expression of Gadd45γ is dependent on a signaling pathway mediated by the tyrosine kinase Jak3 and the transcription factors Stat5a and Stat5b (signal transducer and activator of transcription). Previous studies with ectopically overexpressed Gadd45γ in various cell lines implicated its function in negative growth control. To analyze the physiological role of Gadd45γ we used homologous recombination to generate mice lacking Gadd45γ. Gadd45γ-deficient mice develop normally, are indistinguishable from their littermates, and are fertile. Furthermore, hematopoiesis in mice lacking Gadd45γ is not impaired and Gadd45γ-deficient T lymphocytes show normal responses to IL-2. These data demonstrate that Gadd45γ is not essential for normal mouse development and hematopoiesis, possibly due to functional redundancy among the Gadd45 family members. Gadd45γ is also dispensable for IL-2-induced T-cell proliferation.