Smad4 KO (Smad4 tm1Cxd) Mouse
Mutant Mouse: Smad4
Smad4 knockout: Smad 4 is essential for epiblast proliferation and mesoderm induction in early embryogenesis.
The TGF-β-related superfamily plays an important role in multiple biological systems including embryogenesis. TGF-β ligands activate specific receptors, which interact with specific Smad proteins, which in turn form a complex with a common partner, Smad4, that conveys the signal to downstream targets. Exon 8 of the Smad4 gene was disrupted using homologous recombination in embryonic stem cells. Exon 8 encodes the C-terminal domain of Smad4 that is essential for the formation of heteromeric complexes with the other Smads. Mice heterozygous for the Smad4 mutation are phenotypically normal. Homozygotes, however, die early in embryonic development (day E6.5-8.5). Smad4 is required for three essential functions in early embryogenesis: epiblast proliferation, egg cylinder formation, and mesoderm induction.