Characterization and Targeting of Forkhead Box K2 (FOXK2)

Forkhead/winged-helix transcription factors are evolutionarily conserved and found in organisms as diverse as yeast and humans. They regulate a broad spectrum of events during embryonic and post natal development, including cell cycle regulation, survival, and differentiation. Here we aim at characterizing the function of the murine Forkhead Box k2 transcription factor (Foxk2), which is a member of this large family. We found that it is expressed in various tissues, and is restricted to the nucleus of cells. The main part of this project consisted in the construction of a targeting vector for Foxk2, for the future generation of a conditional knock-out mouse. This would enable us to investigate in details the function of this gene in specific tissues. Several plasmids containing modified versions of Foxk2 cDNA have been constructed as well in order to study in vitro the role of this protein. Finally, a strategy involving a transgenic Bacterial Artificial Chromosome (BAC) has been elaborated to create a reporter mouse for this gene, as well as a lineage tracer. Our intention was to knock-in a Venus PEST IRES Cre-ERT reporter cassette into the starting codon of Foxk2. The Venus gene will allow for a precise study of the expression pattern of Foxk2 in vivo, and the inducible Cre-ERT recombinase will enable us to follow the expression of Foxk2 within the lineage of a particular population of cells