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