Mammalian Genome

, Volume 15, Issue 10, pp 749–758 | Cite as

The Tyr (albino) locus of the laboratory mouse

  • Friedrich BeermannEmail author
  • Seth J. Orlow
  • M. Lynn Lamoreux


The albino mouse was already known in ancient times and was apparently selectively bred in Egypt, China, and Japan. Thus, it is not surprising that the c or albino locus (now the Tyr locus) was among the first used to demonstrate Mendelian inheritance in mammals at the dawn of the past century. This locus is now known to encode tyrosinase, the rate-limiting enzyme in the production of melanin pigment, and the molecular basis of the albino (Tyr c ) mutation is known. Here we describe the congenic series of Tyr-locus alleles, from wild type to null (albino). We compare eye and skin pigmentation phenotypes and the genetic lesions that cause each. We suggest that this panel of congenic mutants contains rich, untapped resources for the study of many questions of basic cell biological interest.


Hair Follicle Tyrosinase Activity Hair Coat Tyrosinase Gene Tyrosinase Enzyme 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Thanks are due to Andrea Schmidt for help with the DNA and RNA analyses of Tyr c-e and Tyr c-a mutant mice. Work in the laboratory of FB was supported by grants from the Swiss Cancer League, by grant 3100-066796.01 from the Swiss National Science Foundation, and by the National Center of Competence in Research (NCCR) Molecular Oncology, a research instrument of the Swiss National Science Foundation, and in the laboratory of SJO by PHS grants EY10223 and AR41880.


  1. Barsh, G 2003What controls variation in human skin color?PLoS Biol1019022CrossRefGoogle Scholar
  2. Beermann, F, Ruppert, S, Hummler, E, Bosch, FX, Müller G,  et al. 1990Rescue of the albino phenotype by introduction of a functional tyrosinase gene into miceEMBO J928192826PubMedGoogle Scholar
  3. Beermann, F, Orlow, SJ, Boissy, RE, Schmidt, A, Boissy, YL,  et al. 1995Misrouting of tyrosinase with a truncated cytoplasmic tail as a result of the murine platinum (cp) mutationExp Eye Res61599607PubMedGoogle Scholar
  4. Bennett, D, Lamoreux, M 2003The color loci of mice —a genetic centuryPigment Cell Res16333344CrossRefPubMedGoogle Scholar
  5. Bentley, NJ, Eisen, T, Goding, CR 1994Melanocyte-specific expression of the human tyrosinase promoter: activation by the microphthalmia gene product and role of the initiatorMol Cell Biol1479968006PubMedGoogle Scholar
  6. Bradl, M, Larue, L, Mintz, B 1991Clonal coat color variation due to a transforming gene expressed in melanocytes of transgenic miceProc Natl Acad Sci USA8864476451PubMedGoogle Scholar
  7. Camacho–Hübner, A, Beermann, F 2001Increased transgene expresssion by the mouse tyrosinase enhancer is restricted to neural crest-derived pigment cellsGenesis29180187CrossRefPubMedGoogle Scholar
  8. Castle, W, Allen, G 1903The heredity of albinismProc Am Acad Arts Sci38603621Google Scholar
  9. Cattanach, B, Rasberry, C 1988Dark-eyed albinismMouse News Lett8164Google Scholar
  10. Chen, K, Manga, P, Orlow, S 2002Pink-eyed dilution protein controls the processing of tyrosinaseMol Biol Cell1319531964CrossRefPubMedGoogle Scholar
  11. Chiu, E, Lamoreux, M, Orlow, S 1993Postnatal ocular expression of tyrosinase and related proteins: disruption by the Pink-eyed Unstable (pun) mutationExp Eye Res57301305CrossRefPubMedGoogle Scholar
  12. Cohen–Solal, K, Reuhl, K, Ryan, K, Roberts, K, Chen, S 2001Development of cutaneous amelanotic melanoma in the absence of a functional tyrosinasePigment Cell Res14466474Google Scholar
  13. Cohen–Solal, K, Crespo–Carbone, S, Namkoong, J, Mackason, K, Roberts, K,  et al. 2002Progressive appearance of pigmentation in amelanotic melanoma lesionsPigment Cell Res15282289CrossRefPubMedGoogle Scholar
  14. Coleman, D 1962Effect of genic substitution on the incorporation of tyrosine into the melanin of the mouse skinArch Biochem Biophys96562568PubMedGoogle Scholar
  15. Costin, G, Valencia, J, Vieira, W, Lamoreux, M, Hearing, V 2003Tyrosinase processing and intracellular trafficking is disrupted in mouse primary melanocytes carrying the underwhite (uw) mutation. A model for oculocutaneous albinism (OCA) type 4J Cell Sci11632033212CrossRefPubMedGoogle Scholar
  16. Marmol, V, Beermann, F 1996Tyrosinase and related proteins in mammalian pigmentationFEBS Lett381165168CrossRefPubMedGoogle Scholar
  17. Deol, M, Truslove, G 1980 Nonrandom distribution of unpigmented melanocytes in the retina of chinchilla-mottled mice and its significance Proc XIth Int Pigment Cell Conf, Sendai, Japan.153157Google Scholar
  18. Detlefsen, J 1921A new mutation in the house mouseAm Naturalist55469473CrossRefGoogle Scholar
  19. Dickie, M 1966PlatinumMouse News Lett3430Google Scholar
  20. Donatien, P, Jeffery, G 2002Correlation between rod photoreceptor numbers and levels of ocular pigmentationInvest Ophthalmol Vis Sci4311981203PubMedGoogle Scholar
  21. Feldman, H 1922A fourth allelomorph in the albino series of miceAm Naturalist56573574CrossRefGoogle Scholar
  22. Fryer, J, Oetting, W, King, R 2003Identification and characterization of a DNase hypersensitive region of the human tyrosinase genePigment Cell Res16679684CrossRefPubMedGoogle Scholar
  23. Ganss, R, Montoliu, L, Monaghan, A, Schütz, G 1994A cell-specific enhancer far upstream of the mouse tyrosinase gene confers high level and copy number-related expression in transgenic miceEMBO J1330833093PubMedGoogle Scholar
  24. Garcia–Borron, J, Solano, F 2002Molecular anatomy of tyrosinase and its related proteins: beyond the histidine-bound metal catalytic centerPigment Cell Res15162173CrossRefPubMedGoogle Scholar
  25. Giebel, LB, Tripathi, RK, King, RA, Spritz, RA 1991A tyrosinase gene missense mutation in temperature-sensitive type I oculocutaneous albinism. A human homologue to the Siamese cat and the Himalayan mouseJ Clin Invest8711191122PubMedGoogle Scholar
  26. Giraldo, P, Martinez, A, Regales, L, Lavado, A, Garcia–Diaz, A,  et al. 2003Functional dissection of the mouse tyrosinase locus control region identifies a new putative boundary activityNucleic Acids Res3162906305CrossRefPubMedGoogle Scholar
  27. Goding, C 2000Mitf from neural crest to melanoma: signal transduction and transcription in the melanocyte lineageGenes Dev1417121728PubMedGoogle Scholar
  28. Green, M 1961Himalayan, a new allele of albino in the mouseJ Hered527375Google Scholar
  29. Grüneberg, H 1952Genetics of the MouseNijhoffThe HagueGoogle Scholar
  30. Guillery, R 1974Visual pathways in albinosSci Am2304454PubMedGoogle Scholar
  31. Guyonneau, L, Murisier, F, Rossier, A, Moulin, A, Beermann, F 2004Melanocytes and pigmentation are affected in Dopachrome tautomerase knockout miceMol Cell Biol2433963403CrossRefPubMedGoogle Scholar
  32. Halaban, R, Moellmann, G, Tamura, A, Kwon, B, Kuklinska, E,  et al. 1988Tyrosinases of murine melanocytes with mutations at the albino locusProc Natl Acad Sci USA8572417245PubMedGoogle Scholar
  33. Halaban, R, Svedine, S, Cheng, E, Smicun, Y, Aron, R,  et al. 2000Endoplasmic reticulum retention is a common defect associated with tyrosinase-negative albinismProc Natl Acad Sci USA9758895894CrossRefPubMedGoogle Scholar
  34. He, L, Eldridge, A, Jackson, P, Gunn, T, Barsh, G 2003Accessory proteins for melanocortin signaling: attractin and mahoguninAnn NY Acad Sci994288298PubMedGoogle Scholar
  35. Hearing, V 1973Tyrosinase activity in subcellular fractions of black and albino miceNat New Biol2458183PubMedGoogle Scholar
  36. Huizing, M, Boissy, R, Gahl, W 2000Hermansky–Pudlak syndrome: vesicle formation from yeast to manPigment Cell Res15405419CrossRefGoogle Scholar
  37. Jeffery, G, Schütz, G, Montoliu, L 1994Correction of abnormal retinal pathways found with albinism by introduction of a functional tyrosinase gene in transgenic miceDev Biol166460464CrossRefPubMedGoogle Scholar
  38. Kidson, S, Fabian, B 1981The effect of temperature on tyrosinase activity in himalayan mouse skinJ Exp Zool2159197PubMedGoogle Scholar
  39. Kwon, B, Halaban, R, Chintamaneni, C 1989aMolecular basis of mouse himalayan mutationBiochem Biophys Res Commun161252260Google Scholar
  40. Kwon, B, Haq, A, Wakulchik, M, Kestler, D, Barton, D,  et al. 1989bIsolation, chromosomal mapping and expression of the mouse tyrosinase geneJ Invest Dermatol93589594CrossRefGoogle Scholar
  41. Lamoreux, M, Pendergast, P 1987Genetic controls over melanocyte differentiation: interaction of agouti-locus and albino-locus genetic defectsJ Exp Zool2437179PubMedGoogle Scholar
  42. Lamoreux, M, Zhou, B, Rosemblat, S, Orlow, S 1995The pinkeyed-dilution protein and the eumelanin/pheomelanin switch: in support of a unifying hypothesisPigment Cell Res8263270PubMedGoogle Scholar
  43. Lamoreux, M, Wakamatsu, K, Ito, S 2001Interaction of major coat color gene functions in mice as studied by chemical analysis of eumelanin and pheomelaninPigment Cell Res142331CrossRefPubMedGoogle Scholar
  44. Land, E, Riley, P 2000Spontaneous redox reactions of dopaquinone and the balance between the eumelanic and phaeomelanic pathwayPigment Cell Res13273277CrossRefPubMedGoogle Scholar
  45. Lavado Judez, A, Montoliu, L 2002Histological, enzymatic and molecular analysis of chinchilla-mottled (Tyrc-m) and extreme dilution mottled (Tyrc-em) mouse mutant tyrosinase allelesPigment Cell Res1563(abstract)Google Scholar
  46. La Vail, J, Nixon, R, Sidman, R 1978Genetic control of retinal ganglion cell projectionsJ Comp Neurol182399421PubMedGoogle Scholar
  47. Lefur, N, Kelsall, SR, Mintz, B 1996Base substitution at different alternative splice donor sites of the tyrosinase gene in murine albinismGenomics37245248CrossRefPubMedGoogle Scholar
  48. Lefur, N, Kelsall, SR, Silvers, WK, Mintz, B 1997Selective increase in specific alternative splice variants of tyrosinase in murine melanomas — a projected basis for immunotherapyProc Natl Acad Sci USA9453325337CrossRefPubMedGoogle Scholar
  49. Libby, R, Smith, R, Savinova, O, Zabaleta, A, Martin, J,  et al. 2003Modification of ocular defects in mouse developmental glaucoma models by tyrosinaseScience29915781581CrossRefPubMedGoogle Scholar
  50. Manga, P, Sato, K, Ye, L, Beermann, F, Lamoreux, M,  et al. 2000Mutational analysis of the modulation of tyrosinase by tyrosinase-related proteins 1 and 2 in vitroPigment Cell Res13364374CrossRefPubMedGoogle Scholar
  51. Markert, C, Silvers, W 1956The effects of genotype and cell environment on melanoblast differentiation in the house mouseGenetics41429450Google Scholar
  52. Moyer, F 1966Genetic variations in the fine structure and ontogeny of mouse melanin granulesAm Zool64366PubMedGoogle Scholar
  53. Newton, J, Cohen–Barak, O, Hagiwara, N, Gardner, J, Davisson, M,  et al. 2001Mutations in the human orthologue of the mouse underwhite gene (uw) underlie a new form of oculocutaneous albinism, OCA4Am J Hum Genet69981988Google Scholar
  54. Orlow, SJ, Boissy, RE, Moran, DJ, Pifko–Hirst, S 1993Subcellular distribution of tyrosinase and tyrosinase-related protein-1: implications for melanosomal biogenesisJ Invest Dermatol1005564CrossRefPubMedGoogle Scholar
  55. Phillips, R 1970Chinchilla-mottledMouse News Lett4226Google Scholar
  56. Porter, SD, Meyer, CJ 1994A distal tyrosinase upstream element stimulates gene expression in neural-crest-derived melanocytes of transgenic mice: position-independent and mosaic expressionDevelopment12021032111PubMedGoogle Scholar
  57. Porter, S, Larue, L, Mintz, B 1991Mosaicism of tyrosinase-locus transcription and chromatin structure in dark vs. light melanocyte clones of homozygous chinchilla-mottled miceDev Genet12393402PubMedGoogle Scholar
  58. Porter, S, Hu, J, Gilks, C 1999Distal upstream tyrosinase S/MAR-containing sequence has regulatory properties specific to subsets of melanocytesDev Genet254048CrossRefPubMedGoogle Scholar
  59. Rachel, R, Dolen, G, Hayes, N, Lu, A, Erskine, L,  et al. 2002aSpatiotemporal features of early neurogenesis differ in wild-type and albino mouse retinaJ Neurosci2242494263Google Scholar
  60. Rachel, R, Mason, C, Beermann, F 2002bInfluence of tyrosinase levels on pigment accumulation in the retinal pigment epithelium and on the uncrossed retinal projectionPigment Cell Res15273281CrossRefGoogle Scholar
  61. Regales, L, Giraldo, P, Garcia–Diaz, A, Lavado, A, Montoliu, L 2003Identification and functional validation of a 5′ upstream regulatory sequence in the human tyrosinase gene homologous to the locus control region of the mouse tyrosinase genePigment Cell Res16685692CrossRefPubMedGoogle Scholar
  62. Riley, PA 1999The great DOPA mystery: The source and significance of DOPA in phase I melanogenesisCell Mol Biol45951960Google Scholar
  63. Rinchik, EM, Stoye, JP, Frankel, WN, Coffin, J, Kwon, BS,  et al. 1993Molecular analysis of viable spontaneous and radiation-induced albino (c)-locus mutations in the mouseMutat Res286199207PubMedGoogle Scholar
  64. Rinchik, E, Bell, J, Hunsicker, P, Friedman, J, Jackson, I,  et al. 1994Molecular genetics of the brown (b)-locus region of mouse chromosome 4. I. Origin and molecular mapping of radiation-and chemical-induced lethal brown deletionsGenetics137845854PubMedGoogle Scholar
  65. Ruppert, S, Müller, G, Kwon, B, Schütz, G 1988Multiple transcripts of the mouse tyrosinase gene are generated by alternative splicingEMBO J727152722PubMedGoogle Scholar
  66. Russell, E 1948A quantitative histological study of the pigment found in the coat color mutants of the house mouse. 2. Estimates of the total volume of pigmentGenetics33228236Google Scholar
  67. Russell, L, Montgomery, C, Raymer, G 1982Analysis of the albino-locus region of the mouse: IV. Characterization of 34 deficienciesGenetics100427453PubMedGoogle Scholar
  68. Schmidt, A, Beermann, F 1994Molecular basis of dark-eyed albinism in the mouseProc Natl Acad Sci USA9147564760PubMedGoogle Scholar
  69. Shibahara, S, Okinaga, S, Tomita, Y, Takeda, A, Yamamoto, H,  et al. 1990A point mutation in the tyrosinase gene of BALB/c albino mouse causing the cysteine–serine substitution at position 85Eur J Biochem189455461PubMedGoogle Scholar
  70. Silvers, WK 1979The coat colors of mice—a model for mammalian gene action and interactionSpringerNew YorkGoogle Scholar
  71. Simmen, T, Schmidt, A, Hunziker, W, Beermann, F 1999The tyrosinase tail mediates sorting to the lysosomal compartment in MDCK cells via a di-leucine and a tyrosine-based signalJ Cell Sci1124553PubMedGoogle Scholar
  72. Sweet, H 1987Acromelanic (c a )Mouse News Lett7856Google Scholar
  73. Takeuchi, S, Takeuchi, T, Yamamoto, H 2000A possible mechanism for feedback regulation of the mouse tyrosinase gene by its 3′ non-coding RNA fragmentsPigment Cell Res13109115CrossRefPubMedGoogle Scholar
  74. Townsend, D, Witkop, CJ, Mattson, J 1981Tyrosinase subcellular distribution and kinetic parameters in wild type and C-locus mutant C57BL/6J miceJ Exp Zool216113119PubMedGoogle Scholar
  75. Townsend, D, Guillery, P, King, R 1985Himalayan tyrosinase does not demonstrate temperature sensitivityBagnara, JKlaus, SPaul, ESchartel, M. eds. Biological, Molecular and Clinical Aspects of PigmentationUniversity of Tokyo PressTokyoGoogle Scholar
  76. Toyofuku, K, Wada, I, Valencia, J, Kushimoto, T, Ferrans, V,  et al. 2001Oculocutaneous albinism types 1 and 3 are ER retention diseases: mutation of tyrosinase or Tyrp1 can affect the processing of both mutant and wild-type proteinsFASEB J1521492161CrossRefPubMedGoogle Scholar
  77. Wakamatsu, K, Ito, S 2002Advanced chemical methods in melanin determinationPigment Cell Res15174183CrossRefPubMedGoogle Scholar
  78. Widlund, H, Fisher, D 2003Microphthalmia-associated transcription factor: a critical regulator of pigment cell development and survivalOncogene2230353041CrossRefPubMedGoogle Scholar
  79. Wu, M, Rinchik, EM, Wilkinson, E, Johnson, DK 1997Inherited somatic mosaicism caused by an intracisternal particle insertion in the mouse tyrosinase geneProc Natl Acad Sci USA94890894CrossRefPubMedGoogle Scholar
  80. Yokoyama, T, Silversides, DW, Waymire, KG, Kwon, BS, Takeuchi, T,  et al. 1990Conserved cysteine to serine mutation in tyrosinase is responsible for the classical albino mutation in laboratory miceNucleic Acids Res1872937298PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Friedrich Beermann
    • 1
    Email author
  • Seth J. Orlow
    • 2
  • M. Lynn Lamoreux
    • 3
  1. 1.ISREC (Swiss Institute for Experimental Cancer Research)National Center of Competence in Research (NCCR)Molecular OncologyEpalingesSwitzerland
  2. 2.The Ronald O. Perelman Department of Dermatology & The Department of Cell BiologyNew York University School of MedicineNew York, New YorkUSA
  3. 3.BryanUSA

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