title: Tyrosinase Depletion Prevents the Maturation of Melanosomes in the Mouse Hair Follicle.
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.
authors.affiliation: Department of Biological Chemistry, University of California Irvine, Irvine, CA, United States of America.
authors.forename: Elyse K
authors.initials: EK
authors.lastname: Paterson
authors.affiliation: University of California Irvine Transgenic Mouse Facility, University Laboratory Animal Resources, Office of Research, Irvine, CA, United States of America.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Fielder
authors.affiliation: Department of Developmental and Cell Biology, University of California Irvine, Irvine, CA, United States of America.
authors.forename: Grant R
authors.initials: GR
authors.lastname: MacGregor
authors.affiliation: Department of Chemistry, Fujita Health University School of Health Sciences, Toyoake, Aichi 470-1192, Japan.
authors.forename: Shosuke
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Chemistry, Fujita Health University School of Health Sciences, Toyoake, Aichi 470-1192, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Wakamatsu
authors.affiliation: Department of Statistics, University of California Irvine, Irvine, CA, United States of America.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Gillen
authors.affiliation: Department of Dermatology, University of Cincinnati, Cincinnati, OH, United States of America.
authors.forename: Victoria
authors.initials: V
authors.lastname: Eby
authors.affiliation: Department of Dermatology, University of Cincinnati, Cincinnati, OH, United States of America.
authors.forename: Raymond E
authors.initials: RE
authors.lastname: Boissy
authors.affiliation: Department of Biological Chemistry, University of California Irvine, Irvine, CA, United States of America.|Department of Dermatology, University of California Irvine, Irvine, CA, United States of America.
authors.forename: Anand K
authors.initials: AK
authors.lastname: Ganesan
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018859:Hair Follicle / Q000166:cytology / Q000378:metabolism*; D008543:Melanins / Q000378:metabolism*; D020460:Melanosomes / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism*; D012880:Skin Pigmentation
chemical_list: D008543:Melanins; D014442:Monophenol Monooxygenase