Tyrosinase Depletion Prevents the Maturation of Melanosomes in the Mouse Hair Follicle.

Elyse K Paterson,Raymond E Boissy,Thomas J Fielder,Grant R Macgregor,Victoria Eby,Anand K Ganesan,Daniel L Gillen,Shosuke Ito,Kazumasa Wakamatsu,Ling Hou

doi:10.1371/journal.pone.0143702

Elyse K Paterson, Raymond E Boissy + Show 8 more

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https://doi.org/10.1371/journal.pone.0143702

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Abstract

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.

Highlights

Skin color varies widely both within and between human ethnic populations, evolving over generations to be darker in indigenous equatorial populations to protect the skin from UV damage [1, 2], or to be lighter in populations at higher latitudes to facilitate Vitamin D production [3]
Lentiviral constructs that expressed Tyr shRNA or non-targeting scrambled shRNA were used to infect B16 mouse melanoma cells at a multiplicity of infection (MOI) of 0.1 to ensure that each cell was only infected with one lentivirus [38]
The tetracycline response element (TRE), GFP, and Tyr-shRNA are all inserted downstream of the Col1a1 locus in chromosome 11 in the KH2 cells (Fig 1B), a C57BL/6J x 129S4 F1 ES cell line that is pre-engineered to express a reverse tet-trans-activator from the ROSA26 locus on chromosome 6 [37]

Summary

Introduction

Skin color varies widely both within and between human ethnic populations, evolving over generations to be darker in indigenous equatorial populations to protect the skin from UV damage [1, 2], or to be lighter in populations at higher latitudes to facilitate Vitamin D production [3]. Lighter skinned populations have moved to more temperate climates, resulting in the increased incidence and prevalence of UV-induced skin cancer.

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