Smad7-modified alleles by various gene-targeting strategies.

Signalling of the transforming growth factor-β (TGF-β) family is tightly regulated by various mechanisms including negative feedback by Inhibitory Sma- and Mad-related proteins (Smads) (I-Smads: Smad6 and Smad7). Smad6 preferentially inhibits bone morphogenetic protein (BMP) signalling, whereas Smad7 suppresses both TGF-β and BMP signalling. To elucidate the roles of Smad7 in murine development and in TGF-β signalling, several Smad7-deficient mouse strains have been generated. Tojo et al. (Smad7-deficient mice show growth retardation with reduced viability. J. Biochem. 2012;151:621-631.) demonstrated that Smad7 null mutation caused perinatal lethality on a C57BL/6 background. However, the Smad7-deficient mice on an ICR background survived to adulthood, but showing growth retardation. Unexpectedly, phosphorylation levels of Smad2 and Smad3 were slightly reduced in murine embryonic fibroblast (MEF) cells isolated from Smad7-deficient embryos compared with wild-type MEF cells. Together with other Smad7-mutant mouse strains, these mutant mice provide useful tools to understand important roles of Smad7 in the development of murine embryos and diseases.