LACK OF IL-4-INDUCED TH2 RESPONSE AND IGE CLASS SWITCHING IN MICE WITH DISRUPTED STAT6 GENE

Signal transducers and activators of transcription (Stats) are activat ed by tyrosine phosphorylation in response to cytokines, and are thoug ht to mediate many of their functional responses(1-4) Stat6 is activat ed in response to interleukin (IL)-4 (refs 5,6) and may contribute to various functions including mitogenesis, T-helper cell differentiation and immunoglobulin isotype switching(7). To evaluate the role of Stat 6, we generated Stat6-null mice (Stat6(-/-)) by gene disruption in emb ryonic stem cells. The mice were viable, indicating the lack of a non- redundant function in normal development. Although naive lymphoid cell development was normal, Stat6(-/-) mice were deficient in IL-4-mediat ed functions including Th2 helper T-cell differentiation, expression o f cell surface markers, and immunoglobulin class switching to IgE. In contrast, IL-4-mediated proliferation was only partly affected.