Conditional expression of Lodavin, an avidin-tagged LDL receptor, for biotin-mediated applications in vivo

Abstract

Lodavin represents an engineered fusion protein that consists of a cytoplasmic and a transmembrane domain of the human low-density lipoprotein receptor coupled to an extracellular avidin monomer. Biotinylated compounds have been successfully targeted to Lodavin-expressing cells that have been transduced by a Lodavin-containing virus, and the targeting is based on the high affinity between biotin and avidin. We engineered a Rosa26 (R26R) knock-in Lodavin mouse to develop biotin-based applications such as targeted drug delivery, cell purification, and tissue imaging in vivo. A cDNA encoding Lodavin was inserted downstream of a floxed βgeo resistance gene in the R26R locus in embryonic stem cells, and a germ line-derived R26RLodavin mouse line was generated. Efficient removal of the floxed βgeo cassette and conditional activation of Lodavin expression was achieved as a result of crossing the R26RLodavin mice with HoxB7-Cre, Wnt4-Cre, or Tie1-Cre mice. In summary, the R26RLodavin mouse line may provide a useful tool for testing and developing applications with the aid of avidin and biotin interaction.