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

Genesis. 2003 Sep;37(1):5-11. doi: 10.1002/gene.10219.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Binding Sites
  • Blotting, Southern
  • DNA-Binding Proteins / genetics*
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism
  • Exons
  • Genetic Vectors
  • Heterozygote
  • In Situ Hybridization
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout*
  • Mice, Transgenic
  • Models, Genetic
  • Natriuretic Agents / metabolism*
  • Phosphoproteins / genetics*
  • Polymerase Chain Reaction
  • Smad5 Protein
  • Stem Cells / cytology
  • Time Factors
  • Trans-Activators / genetics*
  • Transforming Growth Factor beta / metabolism

Substances

  • DNA-Binding Proteins
  • Natriuretic Agents
  • Phosphoproteins
  • Smad5 Protein
  • Smad5 protein, mouse
  • Trans-Activators
  • Transforming Growth Factor beta