title: Stem cell factor rescues tyrosinase expression and pigmentation in discreet anatomic locations in albino mice.
abstract: The K14-SCF transgenic murine model of variant pigmentation is based on epidermal expression of stem cell factor (SCF) on the C57BL/6J background. In this system, constitutive expression of SCF by epidermal keratinocytes results in retention of melanocytes in the interfollicular basal layer and pigmentation of the epidermis itself. Here, we extend this animal model by developing a compound mutant transgenic amelanotic animal defective at both the melanocortin 1 receptor (Mc1r) and tyrosinase (Tyr) loci. In the presence of K14-Scf, tyrosinase-mutant animals (previously thought incapable of synthesizing melanin) exhibited progressive robust epidermal pigmentation with age in the ears and tails. Furthermore, K14-SCF Tyr(c2j/c2j) animals demonstrated tyrosinase expression and enzymatic activity, suggesting that the c2j Tyr defect can be rescued in part by SCF in the ears and tail. Lastly, UV sensitivity of K14-Scf congenic animals depended mainly on the amount of eumelanin present in the skin. These findings suggest that c-kit signaling can overcome the c2j Tyr mutation in the ears and tails of aging animals and that UV resistance depends on accumulation of epidermal eumelanin.
authors.affiliation: Department of Pediatrics, University of Kentucky College of Medicine, the Markey Cancer Center, the Graduate Center for Toxicology, Lexington, KY, USA.
authors.forename: Jillian C
authors.initials: JC
authors.lastname: Vanover
authors.forename: Malinda L
authors.initials: ML
authors.lastname: Spry
authors.forename: Laura
authors.initials: L
authors.lastname: Hamilton
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Wakamatsu
authors.forename: Shosuke
authors.initials: S
authors.lastname: Ito
authors.forename: John A
authors.initials: JA
authors.lastname: D'Orazio
mesh_terms: D000818:Animals; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism / Q000528:radiation effects; D006200:Hair Color / Q000502:physiology; D006801:Humans; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D012880:Skin Pigmentation / Q000502:physiology*; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D019089:Stem Cell Factor; D014442:Monophenol Monooxygenase; D019009:Proto-Oncogene Proteins c-kit
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