Endothelin 3 induces skin pigmentation in a keratin-driven inducible mouse model

Roman J. Garcia, Avner Ittah, Sheyla Mirabal, Jessica Figueroa, Lidice Lopez, Adam B. Glick, Lidia Kos

Research output: Contribution to journalArticle

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Abstract

Endothelin 3 (Edn3) encodes a ligand important to developing neural crest cells and is allelic to the spontaneous mouse mutation occurring at the lethal spotting (ls) locus. Edn3ls/ls mutants exhibit a spotted phenotype due to reduced numbers of neural crest-derived melanocyte precursors in the skin. In this study, we show that when Edn3 is driven by the keratin 5 promoter and thereby placed proximal to melanocyte lineage cells, adult mice manifest pigmented skin harboring dermal melanocytes. Using a tetracycline inducible system, we show that the postnatal expression of Edn3 is required to maintain these dermal melanocytes, and that early expression of the Edn3 transgene is important to the onset of the hyperpigmentation phenotype. Crosses into Edn3ls/ls mutants demonstrate that the Edn3 transgene expression does not fully compensate for the endogenous expression pattern. Crosses into tyrosine kinase receptor KitWv mutants indicate that Edn3 can partially compensate for Kit's role in early development. Crosses into A y mutant mice considerably darkened their yellow coat color suggesting a previously unreported role for endothelin signaling in pigment switching. These results demonstrate that exogenous Edn3 affects both precursors and differentiated melanocytes, leading to a phenotype with characteristics similar to the human skin condition dermal melanocytosis.

Original languageEnglish (US)
Pages (from-to)131-142
Number of pages12
JournalJournal of Investigative Dermatology
Volume128
Issue number1
DOIs
StatePublished - Jan 2008

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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