Stem cell factor rescues tyrosinase expression and pigmentation in discreet anatomic locations in albino mice
| Autor: | Laura Hamilton, Shosuke Ito, John A. D'Orazio, Jillian C. Vanover, Kazumasa Wakamatsu, Malinda Spry |
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| Rok vydání: | 2009 |
| Předmět: |
Ultraviolet Rays
Transgene Tyrosinase Stem cell factor Mice Transgenic Skin Pigmentation Dermatology Biology General Biochemistry Genetics and Molecular Biology Article Melanin Mice Animals Humans Hair Color Genetics Stem Cell Factor Epidermis (botany) integumentary system Monophenol Monooxygenase Cell biology Mice Inbred C57BL Proto-Oncogene Proteins c-kit Phenotype Oncology Epidermal Cells Melanocytes Signal transduction Epidermis Melanocortin 1 receptor Signal Transduction |
| Zdroj: | Pigment cellmelanoma research. 22(6) |
| ISSN: | 1755-148X |
| Popis: | We previously reported a transgenic animal model of variant pigmentation based on epidermal expression of stem cell factor (SCF) and well-characterized coat color genes bred into the C57Bl/6 background. In this system, constitutive expression of SCF by epidermal keratinocytes results in the maintenance of epidermal melanocytes in the interfollicular basal epidermal layer and subsequent pigmentation of the epidermis itself. In this report, we describe extending this animal model by developing a compound mutant transgenic amelanotic animal defective at both the melanocortin 1 receptor (Mc1r) and tyrosinase (Tyr) loci. We have observed SCF-dependent pigment deposition in specific anatomic regions regardless of tyrosinase (Tyr) or Mc1r genetic status. Thus, in the presence of K14-Scf, tyrosinase-null animals (previously thought incapable of synthesizing melanin) exhibited progressive robust epidermal pigmentation with age in the ears and tails. Furthermore, in the presence of the K14-Scf transgene, Tyr-defective animals demonstrated tyrosinase activity, suggesting that the c2j Tyr promoter defect is leaky and that Tyr expression can be rescued in part by SCF in the ears and tail. Lastly, we found that UV sensitivity of K14-Scf congenic animals differing only at the Mc1r or Tyr loci depended mainly on the amount of eumelanin present in the skin. These findings suggest that c-kit signaling can overcome the c2j Tyr promoter mutation in the ears and tails of aging animals but that UV resistance depends on accumulation of epidermal eumelanin. |
| Databáze: | OpenAIRE |
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