Fig. 6. Histological and microscopic analyses of skin of mtDNA-depleter mice.

a Hematoxylin- and eosin-stained sections of dorsal skin from wild-type control (n = 3) (i and ii) and mtDNA-depleter mice (n = 3) (iii–-vi) after 2 months of continuous dox induction. While the skin of wild-type mice shows the presence of normal skin histology (i, ×10), the skin of mtDNA-depleter mice shows hyperplastic epidermis with hyperkeratosis (black color arrow), dysfunctional hair follicles containing keratinaceous debris and/or malformed hair (yellow color arrow), and increased the number of inflammatory cells in the dermis (arrowhead) (iii, ×10). Skin sections at higher magnification show the presence of normal telogen hair follicles (ii, ×40) in wild-type control mice and aberrant telogen (iv, ×40) and anagen hair follicles (vi, ×20) with defective sebaceous glands. Panel v shows ruptured follicular cyst surrounded by granulomatous and mixed inflammatory infiltrate in mtDNA-depleter mice. b–d Quantification of epidermal thickness (b), hair follicles in telogen (c), and anagen (d) stages of hair cycle (mean ± s.e.m; *P<0.05, Student’s t test) in skin samples from wild-type control (n = 3) and mtDNA-depleter (n = 3) mice after 2 months of continuous dox induction. e Representative images of PCNA immuno-stained cross-sections of skin from wild-type control (n = 3) and mtDNA-depleter mice (n = 3) after 2 months of dox induction. The basement membrane position in these images is marked with dotted lines. f Quantification of epidermal proliferation (PCNA⁺) in skin samples from wild-type control (n = 3) and mtDNA-depleter (n = 3) mice after 2 months of continuous dox induction. g Electron micrographs of skin samples from wild-type control (n = 3) and mtDNA-depleter mice (n = 3) after 2 months of dox induction. Skin from mtDNA-depleter mice revealed a severely disturbed mitochondrial structure with loss of cristae and degeneration of intramitochondrial structures. Depleter = mtDNA-depleter mice