a, Schematic of whole-mount views of scale (orange) and interscale (green) areas in mouse tail epidermis. b, Representative whole-mount images of pigment distribution in the tail epidermis from young (8 wo) and aged (22 mo) mice; bottom, enlarged views of dashed outlines. Similar results were obtained in at least three independent experiments. c, GO analysis between total epidermal cells from young (7–8 wo, n = 3) and aged (22–25 mo, n = 3) mice for ≥twofold-downregulated genes in aged total epidermal cells. The GO terms for melanocyte-related genes (asterisks) were significantly enriched in young epidermal cells. d, Heat map showing the fold change (expressed as a log) between total epidermis from young (7–8 wo, n = 3) and aged (22–25 mo, n = 3) mice for melanocyte-related genes such as Mitf, Tyrp1, Sox10 and Dct. e, Representative immunofluorescence image of KIT+ melanocytes in Dct–H2B–GFP+ tg mice. Dct–H2B–GFP+ was merged with KIT+ in epidermal melanocytes and melanoblasts. Data are representative of at least ten independent experiments. f, Representative tail whole-mount immunofluorescence images of melanocyte distribution and KRT31 expression in skin from 7-wo and 22-mo Dct-H2B-GFP tg mice. Dashed line, margin of scale area. g, Numbers of GFP-marked melanocytes per scale area from young (7 wo, n = 29 scales) and aged (22 mo, n = 24) Dct-H2B-GFP tg mice. Dct–H2B–GFP+ melanocytes were significantly decreased during ageing. h, Representative images of tail skin after deletion of Col17a1 and/or Itga6. We treated 7-wo wild-type (control), Col17a1 cKO, Itga6fl/fl;K14-creERT2 (Itga6 cKO) or Col17a1fl/fl;Itga6fl/fl;K14-creERT2 (Col17a1, Itga6 dcKO) mice with TAM to delete each gene in epidermal basal keratinocytes. Arrows, hyperpigmentation; arrowheads, hypopigmentation. i, Representative immunofluorescence images of COL17A1 and ITGA6 in the tail scale area from cont, Col17a1 cKO, Itga6 cKO and Col17a1, Itga6 dcKO (11 wo) mice. Data are representative of at least three independent experiments. j, Representative combined immunofluorescence and bright field (melaninhigh/low) images of GFP at 16 wo from control and Col17a1 or Itga6 cKO mice. Arrows indicate epidermal melanocytes among tail scale basal keratinocytes. k, Numbers of GFP-marked melanocytes per tail scale area (melaninhigh/low) from control (n = 5), Col17a1 cKO (n = 4) and Itga6 cKO (n = 6) combined with Dct-H2B-GFP tg mice. Melaninhigh scale areas from Col17a1 or Itga6 cKO mice showed no significant difference in the number of GFP-marked melanocytes, whereas melaninlow scale areas from Col17a1 or Itga6 cKO mice showed a significant decrease in the number of GFP-marked melanocytes. l, o, Representative images of tail skin from control and UVB-exposed mice at 7 wo, 11 wo and 15 wo (l) or wild-type mice and hCOL17A1 tg mice at 8 wo, 18 mo and 25 mo (o). Repetitive UVB exposure induced hyper-pigmentation (arrows) in a month at 11 wo followed by appearance of depigmented spots upon the cessation of UVB irradiation (arrowheads) at 15 wo. Expression of the hCOL17A1 transgene rescued the age-associated epidermal dyspigmentation. m, Representative ultrastructural images of scale basal cells from control (11 wo) and Col17a1 cKO (11 wo) mice assessed by TEM. Bottom, enlarged views of dashed boxed areas. White lines, show regions across the hemidesmosome, lamina lucida and lamina densa. n, Intensity histograms (above lines) for hemidesmosomes in m. Similar results were obtained in at least three independent experiments. Images are representative of at least five independent experiments (h, l, o). Mean ± s.e.m.; modified Fisher’s exact test (c), two-tailed Mann–Whitney U-test (g) or one-way ANOVA with Dunnett’s post hoc test (k). Source data