| First Author | Tojo M | Year | 2012 |
| Journal | J Biochem | Volume | 151 |
| Issue | 6 | Pages | 621-31 |
| PubMed ID | 22383537 | Mgi Jnum | J:287775 |
| Mgi Id | MGI:6423655 | Doi | 10.1093/jb/mvs022 |
| Citation | Tojo M, et al. (2012) Smad7-deficient mice show growth retardation with reduced viability. J Biochem 151(6):621-31 |
| abstractText | Smad7 is an inhibitory molecule induced by members of the transforming growth factor-beta (TGF-beta) family, including TGF-beta, activin, nodal and bone morphogenetic proteins (BMPs). To elucidate the in vivo functions of Smad7, we generated conditional Smad7-knockout mice in which the Mad homology 2 (MH2) domain and the poly (A) signal sequence were flanked with loxP sites (floxed). The Smad7-floxed mice exhibited no obvious phenotype. Smad7 total-null mice on a C57BL/6 background died within a few days of birth, whereas mice with an ICR background developed to adulthood but were significantly smaller than wild-type mice. Unexpectedly, phospho-Smad2 and phospho-Smad3 were decreased in Smad7-deficient mouse embryonic fibroblast (MEF) cells, whereas phospho-Smad1/5/8 was similarly expressed in wild-type and Smad7-deficient MEF cells. Moreover, expression levels of TGF-beta type I receptor (ALK5) were higher in Smad7-deficient MEF cells than in wild-type MEF cells. Plasminogen activator inhibitor-1 (PAI-1) and inhibitor of differentiation-1 (Id-1) mRNA were similarly expressed in wild-type and Smad7-deficient MEF cells. Some differences were observed in mitogen-activated protein kinase (MAPK)-signalling between wild-type and Smad7-deficient MEF cells. We demonstrated that Smad7 plays an important role in normal mouse growth and provide a useful tool for analysing Smad7 functions in vivo. |
