Lothar Hennighausen (NIDDK)
Floxed Bcl-x: Conditional knockout of pro-survival Bcl-x in primordial germ cells was used to study the balance between pro-apoptotic Bax during embryogenesis.
Bcl-x is a pro-survival protein that opposes the pro-apoptotic action of Bax which interacts with mitochondria to activate the caspase 9 pathway. Mice in which the Bcl-x gene is inactivated die at E12.5. To be able to study lineage-specific activities of Bcl-x at different stages of development, the Cre-LoxP recombination system was used. Homologous recombination was used to flank the promoter, exon1, and major coding exon2 of the Bcl-x gene with loxP sites. The targeted allele contained a loxP flanked (or floxed) neomycin cassette in the Bcl-x promoter, and an additional loxP site in intron 2. Floxed Bcl-x has been used to study the balance between Bcl-x and Bax in primordial germ cells that undergo controlled levels of cell reduction due to apoptosis, the induction of hemolytic anemia and splenomegaly following conditional deletion of the Bcl-x gene from erythroid cells, the protection of hepatocytes from apoptosis and ensuing fibrotic response by Bcl-x, and the demonstration that Bcl-x is critical for the survival of dendritic cells, important regulators of immune function.