F1A‐CreERT2 Mice: Targeting and Tracing Cardiomyocytes with Fgf1 Expression in Adult Mouse

Abstract

Fibroblast growth factor 1 (FGF1) regulates many biological and homeostatic processes, including obesity and metabolic syndrome. In mice, Fgf1 gene contains at least three upstream promoters and their respective adjacent untranslated exons that spliced to the first protein coding exon mutually exclusively, giving rise to different Fgf1 mRNA variants. Among them, the Fgf1A transcript is predominantly expressed in the heart. FGF1 can induce cardiomyocyte regeneration and cardiogenesis in vitro and in vivo. Here, we generated a novel mouse line Fgf1A promoter (F1A)‐driven inducible Cre recombinase (CreERT2). We firstly demonstrated that the highest mRNA expression of CreERT2 were detected in the heart specifically of F1A‐CreERT2 mice, similar to that of Fgf1A mRNA. The F1A‐CreERT2 mice were crossed with ROSA26 mice, and the F1 mice were analyzed. The LacZ‐positive signals were detected exclusively in the heart after tamoxifen administration. The CreERT2‐mediated recombination in the tissues is monitored through LacZ‐positive signals, indicating the in situ localization of F1A‐positive cells. Consistently, these F1A‐positive cells with RFP‐positive signals or LacZ‐positive blue signals were co‐localized with cardiomyocytes expressing cardiac troponin T, suggesting cardiomyocyte‐specific activation of Fgf1A promoter. Our data suggested that the F1A‐CreERT2 mouse line could be used for time‐dependent and lineage tracing of Fgf1A‐expressing cells in vivo. F1A‐CreERT2 line is a valuable tool for in vivo lineage tracing of Fgf1A‐expressing cells during heart development and will facilitate the elucidation of the physiological and pathological role of Fgf1A in heart failure and metabolic syndrome.