Alteration of the <i>Tg(DctSox10)</i> phenotype through the reduction of <i>Mitf</i>.

Abstract

<p>(A–B) Comparison of <i>Tg(DctSox10)/Tg(DctSox10)</i> and <i>Tg(DctSox10)/Tg(DctSox10); Mitf<sup>vga9/+</sup></i> animals at P70. Addition of the <i>Mitf<sup>vga9/+</sup></i> allele reduces the congenital hypopigmentation seen in <i>Tg(DctSox10)/Tg(DctSox10)</i> animals, and is evident in dorsal views (loss of back spotting) and in ventral views (reduction in belly spot size). Premature hair graying of <i>Tg(DctSox10)</i> homozygotes seen at p70 is retained with <i>Mitf<sup>vga9</sup></i> (n = 6). (C) <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003644#s1" target="_blank">Introduction</a> of <i>Sox10<sup>lacZ</sup></i> into <i>Tg(DctSox10)/Tg(DctSox10)</i> homozygotes partially rescues both congenital white spotting and premature hair graying (n = 2). (D) At 40 weeks of age, <i>Tg(DctSox10)/+; Mitf<sup>vga9/+</sup></i> double heterozygotes exhibit visibly increased hair graying in comparison to <i>Tg(DctSox10)/+</i>. (E) Hair graying severity was determined in animals 6–10 weeks of age by quantitating the number of non-pigmented anagen III/IV hair bulbs in +/+, <i>Tg(DctSox10)/+, Tg(DctSox10)/+; Mitf<sup>vga9/+</sup></i>, and <i>Mitf<sup>vga9/+</sup></i> skins after plucking and harvesting at 7dpp. <i>Tg(DctSox10)/+; Mitf<sup>vga9/+</sup></i> mice exhibit a significant increase in non-pigmented hair bulbs in comparison to the single heterozygotes or +/+ animals (**p<0.0015). <i>Tg(DctSox10)/+</i> animals also produce more non-pigmented hair bulbs in comparison to +/+ and <i>Mitf<sup>vga9/+</sup></i> animals (*p<0.002). (F) <i>Tg(DctSox10)/+; Mitf<sup>vga9/+</sup></i> animals (from E) display extensive ectopic pigmentation within the LPP of their hair follicles beyond what is normally observed in <i>Tg(DctSox10)/+</i> animals (arrows, n = 4). (G) Number of LPP melanocytes per anagen III/IV hair follicle in <i>Tg(DctSox10)/+, Tg(DctSox10)/+; Mitf<sup>vga9/+</sup>, Mitf<sup>vga9/+</sup></i> animals (from E) that double label for DCT, TRP1, and produce ectopic pigmentation. Hairs from <i>Tg(DctSox10)/+; Mitf<sup>vga9/+</sup></i> animals exhibit significantly more TRP1<sup>+</sup>/PIG<sup>+</sup> LPP melanocytes than in either single heterozygote (*p<0.0125).</p

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