Paterson Elyse K, Fielder Thomas J, MacGregor Grant R, Ito Shosuke, Wakamatsu Kazumasa, Gillen Daniel L, Eby Victoria, Boissy Raymond E, Ganesan Anand K
Department of Biological Chemistry, University of California Irvine, Irvine, CA, United States of America.
University of California Irvine Transgenic Mouse Facility, University Laboratory Animal Resources, Office of Research, Irvine, CA, United States of America.
PLoS One. 2015 Nov 30;10(11):e0143702. doi: 10.1371/journal.pone.0143702. eCollection 2015.
The mechanisms that lead to variation in human skin and hair color are not fully understood. To better understand the molecular control of skin and hair color variation, we modulated the expression of Tyrosinase (Tyr), which controls the rate-limiting step of melanogenesis, by expressing a single-copy, tetracycline-inducible shRNA against Tyr in mice. Moderate depletion of TYR was sufficient to alter the appearance of the mouse coat in black, agouti, and yellow coat color backgrounds, even though TYR depletion did not significantly inhibit accumulation of melanin within the mouse hair. Ultra-structural studies revealed that the reduction of Tyr inhibited the accumulation of terminal melanosomes, and inhibited the expression of genes that regulate melanogenesis. These results indicate that color in skin and hair is determined not only by the total amount of melanin within the hair, but also by the relative accumulation of mature melanosomes.
导致人类皮肤和头发颜色变化的机制尚未完全明了。为了更好地理解皮肤和头发颜色变化的分子调控，我们通过在小鼠中表达针对酪氨酸酶（Tyr）的单拷贝、四环素诱导型短发夹RNA（shRNA）来调节Tyr的表达，Tyr控制着黑色素生成的限速步骤。尽管酪氨酸酶（TYR）的减少并未显著抑制小鼠毛发中黑色素的积累，但适度降低TYR足以改变黑色、刺豚鼠色和黄色毛色背景下小鼠皮毛的外观。超微结构研究表明，Tyr的减少抑制了终末黑素小体的积累，并抑制了调节黑色素生成的基因的表达。这些结果表明，皮肤和头发的颜色不仅取决于毛发中黑色素的总量，还取决于成熟黑素小体的相对积累。
