Abstract
The Smad genes are the intracellular mediators of TGF-beta signals. Targeted mutagenesis in mice has yielded valuable new insights into the functions of this important gene family. These experiments have shown that Smad2 and Smad4 are needed for gastrulation, Smad5 for angiogenesis, and Smad3 for establishment of the mucosal immune response and proper development of the skeleton. In addition, these experiments have shown us the importance of gene dosage in this family, as several of its members yielded haploinsufficiency phenotypes. These include gastrulation and craniofacial defects for Smad2, accelerated wound healing for Smad3, and the incidence of gastric cancer for Smad4. Combinatorial genetics has also revealed functions of Smads in left/right isomerism and liver development.
MeSH terms
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Animals
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Bone Development
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / immunology*
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DNA-Binding Proteins / metabolism*
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Embryonic and Fetal Development
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Gastrula
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Gene Expression Regulation, Developmental
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Genes, Tumor Suppressor
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Humans
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Immune System / physiology
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Liver / growth & development
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Liver / pathology
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Mammals
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Mice
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Mice, Knockout
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Neoplasms / genetics
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Neovascularization, Physiologic / genetics
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Nodal Protein
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Phosphoproteins / genetics
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Phosphoproteins / metabolism
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Smad2 Protein
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Smad3 Protein
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Smad4 Protein
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Smad5 Protein
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Trans-Activators / genetics*
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Trans-Activators / immunology*
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Trans-Activators / metabolism*
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / metabolism
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Wound Healing
Substances
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DNA-Binding Proteins
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NODAL protein, human
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Nodal Protein
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Nodal protein, mouse
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Phosphoproteins
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SMAD2 protein, human
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SMAD3 protein, human
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SMAD4 protein, human
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SMAD5 protein, human
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Smad2 Protein
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Smad2 protein, mouse
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Smad3 Protein
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Smad3 protein, mouse
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Smad4 Protein
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Smad4 protein, mouse
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Smad5 Protein
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Smad5 protein, mouse
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Trans-Activators
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Transforming Growth Factor beta