Generation of a floxed allele of Smad5 for cre-mediated conditional knockout in the mouse

SMAD5 is a member of the Smad Family of intracellular mediators of BMP signals and in endothelial cells of TGF-beta signals. We and Others previously showed that loss of SMAD5 in the mouse results in embryonic lethality (between E9.5-E11.5) due to multiple embryonic and extraembryonic defects. To circumvent the early embryonic lethality and to allow tissue- and time-specific SMAD5 inactivation, we created a conditional SMAD5 allele in the mouse. Floxed SMAD5 (SMAD5(flE2,Neo/flE2,Neo)) mice were generated in which both exon2 and the Neo-cassette were flanked by loxP sites. Here we demonstrate that embryos with ubiquitous Cre-mediated deletion of SMAD5 (SMAD5(flDeltaE2/flDeltaE2)) phenocopy the conventional SMAD5 knockout mice. SMAD5(flE2/flE2) mice are now available and will be a valuable tool to analyze the role of SMAD5 beyond its crucial early embryonic function throughout development and postnatal life.