PMID:10064594

Citation	Yang, X, Letterio, JJ, Lechleider, RJ, Chen, L, Hayman, R, Gu, H, Roberts, AB and Deng, C (1999) Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF-beta. EMBO J. 18:1280-91
Abstract	SMAD3 is one of the intracellular mediators that transduces signals from transforming growth factor-beta (TGF-beta) and activin receptors. We show that SMAD3 mutant mice generated by gene targeting die between 1 and 8 months due to a primary defect in immune function. Symptomatic mice exhibit thymic involution, enlarged lymph nodes, and formation of bacterial abscesses adjacent to mucosal surfaces. Mutant T cells exhibit an activated phenotype in vivo, and are not inhibited by TGF-beta1 in vitro. Mutant neutrophils are also impaired in their chemotactic response toward TGF-beta. Chronic intestinal inflammation is infrequently associated with colonic adenocarcinoma in mice older than 6 months of age. These data suggest that SMAD3 has an important role in TGF-beta-mediated regulation of T cell activation and mucosal immunity, and that the loss of these functions is responsible for chronic infection and the lethality of Smad3-null mice.
Links	PubMed PMC1171218 Online version:10.1093/emboj/18.5.1280
Keywords	Animals; B-Lymphocytes/metabolism; Chemotaxis/drug effects; DNA-Binding Proteins/genetics; Gene Targeting; Immunity, Mucosal/genetics; Immunoglobulin A/metabolism; Intestinal Mucosa/pathology; L-Selectin/analysis; Mice; Mice, Knockout; Neutrophils/metabolism; Signal Transduction/genetics; Smad2 Protein; Smad3 Protein; T-Lymphocytes/drug effects; T-Lymphocytes/metabolism; Trans-Activators/genetics; Transforming Growth Factor beta/pharmacology
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