title: Smad7-deficient mice show growth retardation with reduced viability.
abstract: Smad7 is an inhibitory molecule induced by members of the transforming growth factor-β (TGF-β) family, including TGF-β, 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-β 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.
authors.affiliation: Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Tojo
authors.forename: Ai
authors.initials: A
authors.lastname: Takebe
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Imamura
authors.forename: Kohei
authors.initials: K
authors.lastname: Miyazono
authors.forename: Tomoki
authors.initials: T
authors.lastname: Chiba
mesh_terms: D000818:Animals; D001835:Body Weight; D002478:Cells, Cultured; D006130:Growth Disorders / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D051906:Smad7 Protein / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D051906:Smad7 Protein; C497807:Smad7 protein, mouse