Smad3 KO (Smad3 tm1Cxd) Mouse
Mutant Mouse: Smad3 (MAD homolog 3 (Drosophila))
Smad 3 knockout: Increased susceptibility to opportunistic infections and massive abscesses result from impaired TGF-β-mediated regulation of T cell activation and mucosal immunity.
Smad3 is one of the intracellular mediators that transduce signals from transforming growth factor beta (TGF-β) and activin receptors to the common Smad, Smad4. Targeted disruption of exon 8 in the Smad3 gene deletes a C-terminal region of the protein that is essential for interacting with the TGF-β receptor. The Smad3 null mice are viable at birth, but at weaning develop a progressive and ultimately lethal illness characterized by massive abscesses caused by bacteria that only are infectious in the context of immune deficiency. The immune defect is attributed to abnormalities in mutant T cells and neutrophils. Mutant T cells exhibited an activated phenotype in vivo, and were resistant to inhibition by TGF-β. Mutant neutrophils were impaired in their chemotactic response to TGF-β. Smad-3 plays an important role in TGF-β-mediated regulation of T cell activation and mucosal immunity that can increase susceptibility to opportunistic infection.