Characterization of a novel Fibroblast growth factor 10 (Fgf10) knock-in mouse line to target mesenchymal progenitors during embryonic development

Fibroblast growth factor 10 (Fgf10) is a key player for branching morphogenesis in murine embryos. Fgf10-knockout mice suffer from lung and limb agenesis as well as cecal and colonic atresia and are thus not viable. To date, the Mlcv1v-nLacZ-24 transgenic mouse strain (often referred to as Fgf10LacZ), in which a LacZ cassette has been inserted within regulatory sequences 114 kb upstream of the endogenous Fgf10 gene, has been the only strain that allows transient lineage tracing of Fgf10-positive cells. Here, we describe a novel Fgf10Cre-ERT2 knock-in line (or simply Fgf10iCre) in which a Cre-ERT2-IRES-YFP cassette has been introduced in frame with the first ATG of exon 1 of the endogenous Fgf10 gene. Our studies show that the insertion of Cre-ERT2 has led to Fgf10 inactivation. By crossing the Fgf10iCre line with a Tomatoflox reporter strain, we demonstrate that Fgf10-positive cells are specifically labeled upon tamoxifen administration in many tissues both during development and postnatally. Moreover, we show that the Fgf10iCre line can be used for conditional gene inactivation in an inducible fashion during early developmental stages. We also provide evidence that transcription factors located in the first intron of Fgf10 gene are critical for maintaining Fgf10 expression over time.

Keywords: Fgf10iCre; Fgf10-positive cells; tamoxifen