Generation of an Frs2α conditional null allele

The fibroblast growth factor (FGF) signaling family controls a broad spectrum of cellular processes in development and adult tissue homeostasis and function, which is expressed in almost all tissues at all stages. FGF receptor substrate 2 alpha (FRS2 alpha) is an adaptor protein that recruits downstream substrates to the FGF receptor (FGFR) tyrosine kinase. Disruption of Frs2 alpha gene in mice abrogates activation of the mitogen-activated protein kinase pathway by the FGFR and leads to embryonic lethality at day E7.5 post copulation. To circumvent the embryonic lethality resulting from disruption of the Frs2 alpha gene, which hinders further characterization of the role of FRS2 alpha in adult tissue function and homeostasis, we generated an Frs2 alpha conditional null allele for temporally- and tissue-specific disruption of the Frs2 alpha gene. Using gene targeting in mouse embryonic stem cells, we introduced two loxP sites flanking the largest coding exon, exon 5, in the Frs2 alpha allele. Our results indicate that the floxed Frs2(X (Frs2otflox) allele is a true conditional null allele that encodes wilcitype activity and is converted to a null allele after Cre recombinase mediated recombination.