a-b, Unlike vehicle, subcutaneous ABT-737 treatment of Tyr-NrasQ61K mice at P10 and P12 decreased fur pigmentation and reduced anagen HFs at P56 (a). Anagen HFs are quantified in (b). In b, n=21; P = 0.0000454. c-e, Effect of ABT-737 treatment on melanocytes, bulge stem cells and hair cycle status. c, On cytometry at P56, the percentage of TRP2+/Annexin V+ melanocytes in Tyr-NrasQ61K mice significantly increased in response to ABT-737 treatment at P10-12. In c, n = 5; P = 0.0001816. d, On cytometry at P56, the abundance of CD34+/CD49f+ bulge stem cells in Tyr-NrasQ61K mice was unchanged by ABT-737 treatment at P10-12. In d, n = 5; P = 0.7891838. e, ABT-737 treatment at P10-12 did not affect normal anagen timing in WT mice – skin from both vehicle and ABT-737 treated animals contained HFs in anagen at P33. In e, n = 7; P = 0.2898739. In (c, d, e) representative data is shown on the left, and data quantification – on the right. f–j, Mice with non-nevus expansion in melanocytes display normal hair cycle timing. f–i, Similar to control mice, K14-Edn3 mice with dermal melanocyte expansion (f, g) and K14-Kitl mice with epidermal melanocyte expansion (h, i) were in synchronized anagen at P36 (f, h) and synchronized telogen at P56 (g, i). j, After tamoxifen induction at P12-14, Tyr-CreER;p53fl/fl mice with melanocyte-specific deletion of p53, did not form nevi and exhibited telogen HFs at P56, analogous to induced control mice. In b, n = biologically independent samples. In c, d, e
n = independent experiments. Data are mean ± s.d. P values are calculated using unpaired two-tailed Student’s t-test. NS, P ≥ 0.05, *P ≤ 0.05, **P ≤ 0.01. Scale bars, f–j (wholemount) – 1 mm; a, f–j (histology) – 200 μm; e – 100 μm.
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