Generation of the Krt24-CreERT2 Mouse Line Targeting Outer Bulge Hair Follicle Cells

Outer bulge (OB) hair follicle stem cells (HFSCs) play a crucial role in maintaining hair follicle structural stability and regulating the hair follicle cycle. Previous studies demonstrated that keratin 24 (Krt24) exhibits spatiotemporally restricted expression in OB HFSCs. Here, we report the generation of the Krt24-Cre(ERT2) mouse line. When crossed with Rosa26(LSL-tdTomato) or Rosa26(LSL-DTR) reporter lines, offspring exhibited specific labeling (Krt24-Cre(ERT2);Rosa26(LSL-tdTomato)) or ablation (Krt24-Cre(ERT2);Rosa26(LSL-DTR)) of Krt24(+) cells. In Krt24-Cre(ERT2);Rosa26(LSL-tdTomato) mice, phase-specific tamoxifen (TAM) administration demonstrated spatiotemporal fidelity of Cre activity to endogenous Krt24 expression patterns. Lineage tracing revealed that tdTomato-labeled Krt24(+) cells differentiated into the outer root sheath (ORS) during the anagen phase and persisted when hair follicles reentered telogen. Ablation of Krt24(+) cells via diphtheria toxin (DT) administration significantly delayed anagen initiation. Mice under continuous depletion of Krt24(+) HFSCs experienced substantial mortality after ionizing irradiation. Notably, ionizing radiation triggered a marked expansion of tdTomato-labeled Krt24(+) cells, accompanied by maintained hair follicle homeostasis. Taken together, this study established a Krt24-Cre(ERT2) mouse line targeting OB HFSCs, which are essential for hair follicle development and damage repair.