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Proc Natl Acad Sci U S A. May 1, 1991; 88(9): 3777–3781.
PMCID: PMC51536

The mouse tyrosinase promoter is sufficient for expression in melanocytes and in the pigmented epithelium of the retina.

Abstract

The mouse c locus encodes tyrosinase (monophenol monooxygenase; monophenol, L-dopa:oxygen oxidoreductase, EC 1.14.18.1), the key enzyme in melanin synthesis, which is expressed in the pigment epithelium of the retina and in melanocytes derived from the neural crest. To define regulatory regions of the gene that are important for cell type-specific expression, a deletion series of the tyrosinase 5' region was fused to a chloramphenicol acetyltransferase (CAT) reporter gene and electroporated into tyrosinase-expressing and -nonexpressing cell lines. We show that 270 base pairs 5' of the transcriptional start site is sufficient for CAT expression in a human and a mouse melanoma cell line. This 5' flanking fragment, when cloned in the context of a tyrosinase minigene construct and injected into fertilized eggs of an albino mouse strain, is sufficient for cell type-specific expression in mice. The transgenic mice were pigmented in both skin and eyes. In situ hybridization analysis shows that the 270-base-pair regulatory region contains elements sufficient for specific expression of the transgene both in the pigmented epithelial cells of the retina, which are derived from the optic cup, and in neural crest-derived melanocytes.

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  • Hearing VJ, Jiménez M. Analysis of mammalian pigmentation at the molecular level. Pigment Cell Res. 1989 Mar-Apr;2(2):75–85. [PubMed]
  • Beermann F, Ruppert S, Hummler E, Bosch FX, Müller G, Rüther U, Schütz G. Rescue of the albino phenotype by introduction of a functional tyrosinase gene into mice. EMBO J. 1990 Sep;9(9):2819–2826. [PMC free article] [PubMed]
  • Tanaka S, Yamamoto H, Takeuchi S, Takeuchi T. Melanization in albino mice transformed by introducing cloned mouse tyrosinase gene. Development. 1990 Feb;108(2):223–227. [PubMed]
  • Luckow B, Schütz G. CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements. Nucleic Acids Res. 1987 Jul 10;15(13):5490–5490. [PMC free article] [PubMed]
  • Müller G, Ruppert S, Schmid E, Schütz G. Functional analysis of alternatively spliced tyrosinase gene transcripts. EMBO J. 1988 Sep;7(9):2723–2730. [PMC free article] [PubMed]
  • Taylor JW, Ott J, Eckstein F. The rapid generation of oligonucleotide-directed mutations at high frequency using phosphorothioate-modified DNA. Nucleic Acids Res. 1985 Dec 20;13(24):8765–8785. [PMC free article] [PubMed]
  • Carey TE, Takahashi T, Resnick LA, Oettgen HF, Old LJ. Cell surface antigens of human malignant melanoma: mixed hemadsorption assays for humoral immunity to cultured autologous melanoma cells. Proc Natl Acad Sci U S A. 1976 Sep;73(9):3278–3282. [PMC free article] [PubMed]
  • Boshart M, Weih F, Schmidt A, Fournier RE, Schütz G. A cyclic AMP response element mediates repression of tyrosine aminotransferase gene transcription by the tissue-specific extinguisher locus Tse-1. Cell. 1990 Jun 1;61(5):905–916. [PubMed]
  • de Wet JR, Wood KV, DeLuca M, Helinski DR, Subramani S. Firefly luciferase gene: structure and expression in mammalian cells. Mol Cell Biol. 1987 Feb;7(2):725–737. [PMC free article] [PubMed]
  • Duboule D, Dollé P. The structural and functional organization of the murine HOX gene family resembles that of Drosophila homeotic genes. EMBO J. 1989 May;8(5):1497–1505. [PMC free article] [PubMed]
  • Houghton AN, Eisinger M, Albino AP, Cairncross JG, Old LJ. Surface antigens of melanocytes and melanomas. Markers of melanocyte differentiation and melanoma subsets. J Exp Med. 1982 Dec 1;156(6):1755–1766. [PMC free article] [PubMed]
  • Steel KP, Barkway C. Another role for melanocytes: their importance for normal stria vascularis development in the mammalian inner ear. Development. 1989 Nov;107(3):453–463. [PubMed]
  • Moore KJ, Swing DA, Copeland NG, Jenkins NA. Interaction of the murine dilute suppressor gene (dsu) with fourteen coat color mutations. Genetics. 1990 Jun;125(2):421–430. [PMC free article] [PubMed]
  • Ornitz DM, Palmiter RD, Hammer RE, Brinster RL, Swift GH, MacDonald RJ. Specific expression of an elastase-human growth hormone fusion gene in pancreatic acinar cells of transgenic mice. Nature. 1985 Feb 14;313(6003):600–602. [PubMed]
  • Behringer RR, Mathews LS, Palmiter RD, Brinster RL. Dwarf mice produced by genetic ablation of growth hormone-expressing cells. Genes Dev. 1988 Apr;2(4):453–461. [PubMed]
  • Osborn L, Rosenberg MP, Keller SA, Meisler MH. Tissue-specific and insulin-dependent expression of a pancreatic amylase gene in transgenic mice. Mol Cell Biol. 1987 Jan;7(1):326–334. [PMC free article] [PubMed]
  • Kwon BS, Haq AK, Pomerantz SH, Halaban R. Isolation and sequence of a cDNA clone for human tyrosinase that maps at the mouse c-albino locus. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7473–7477. [PMC free article] [PubMed]
  • Ruppert S, Müller G, Kwon B, Schütz G. Multiple transcripts of the mouse tyrosinase gene are generated by alternative splicing. EMBO J. 1988 Sep;7(9):2715–2722. [PMC free article] [PubMed]
  • Yokoyama T, Silversides DW, Waymire KG, Kwon BS, Takeuchi T, Overbeek PA. Conserved cysteine to serine mutation in tyrosinase is responsible for the classical albino mutation in laboratory mice. Nucleic Acids Res. 1990 Dec 25;18(24):7293–7298. [PMC free article] [PubMed]

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