Expression and Distribution of the Guanine Nucleotide-binding Protein Subunit Alpha-s in Mice Skin Tissues and Its Association with White and Black Coat Colors

  • Yin, Zhihong (College of Animal Science and Veterinary Medicine, Shanxi Agricultural University) ;
  • Zhao, Xin (College of Animal Science and Veterinary Medicine, Shanxi Agricultural University) ;
  • Wang, Zhun (College of Animal Science and Veterinary Medicine, Shanxi Agricultural University) ;
  • Li, Zhen (College of Animal Science and Veterinary Medicine, Shanxi Agricultural University) ;
  • Bai, Rui (College of Animal Science and Veterinary Medicine, Shanxi Agricultural University) ;
  • Yang, Shanshan (College of Animal Science and Veterinary Medicine, Shanxi Agricultural University) ;
  • Zhao, Min (Shaanxi Animal Health Inspection) ;
  • Pang, Quanhai (College of Animal Science and Veterinary Medicine, Shanxi Agricultural University)
  • Received : 2015.08.30
  • Accepted : 2016.01.05
  • Published : 2016.10.01


Guanine nucleotide-binding protein subunit alpha-s ($Gn{\alpha}s$) is a small subunit of the G protein-couple signaling pathway, which is involved in the formation of coat color. The expression level and distribution of $Gn{\alpha}s$ were detected by quantitative real-time-polymerase chain reaction (qPCR), western blot, and immunohistochemistry to investigate the underlying mechanisms of coat color in white and black skin tissues of mice. qPCR and western blot results suggested that $Gn{\alpha}s$ was expressed at significantly higher levels in black mice compared with that of white mice, and transcripts and protein possessed the same expression in both colors. Immunohistochemistry demonstrated $Gn{\alpha}s$ staining in the root sheath and dermal papilla in hair follicle of mice skins. The results indicated that the $Gn{\alpha}s$ gene was expressed in both white and black skin tissues, and the expression level of $Gn{\alpha}s$ in the two types of color was different. Therefore, $Gn{\alpha}s$ may be involved in the coat color formation in mice.


Mice;Guanine Nucleotide-binding Protein Subunit Alpha-s;Coat Color;Hair Follicle;Skin Tissue;Melanocyte;Pigmentation


Supported by : National Natural Science Foundation of China


  1. Dorshorst, B., C. Henegar, X. Liao, M. Sallman Almen, C. J. Rubin, S. Ito, K. Wakamatsu, P. Stothard, B. Van Doormaal, G. Plastow, G. S. Barsh, and L. Andersson. 2015. Dominant red coat color in holstein cattle is associated with a missense mutation in the coatomer protein complex, subunit alpha (COPA) gene. PLoS One 10:e0128969.
  2. Enshell-Seijffers, D., C. Lindon, E. Wu, M. M. Taketo, and B. A. Morgan. 2010. Beta-catenin activity in the dermal papilla of the hair follicle regulates pigment-type switching. Proc. Natl. Acad. Sci. USA. 107:21564-21569.
  3. Eriksson, T. L., S. P. Svensson, I. Lundstrom, K. Persson, T. P. M. Andersson, and R. G. G. Andersson. 2008. Panax ginseng induces anterograde transport of pigment organelles in Xenopus melanophores. J. Ethnopharmacol. 119:17-23.
  4. Fan, R. W., J. S. Xie, J. M. Bai, H. D. Wang, X. Tian, R. Bai, X. Y. Jia, L. Yang, Y. F. Song, M. Herrid, W. J. Gao, X. Y. He, J. B. Yao, G. W. Smith, and C. S. Dong. 2013. Skin transcriptome profiles associated with coat color in sheep. BMC Genomics 14:389.
  5. Feng, H., Y. Sun, and Q. Wang. 2014. Downregulation of c-Kit/MITF-M in graying hair of juvenile poliosis. Acta Derm. Venereol. 94:484-485.
  6. Garcia-Borron, J. C., B. L. Sanchez-Laorden, and C. Jimenez-Cervantes. 2005. Melanocortin-1 receptor structure and functional regulation. Pigment Cell Res. 18:393-410.
  7. Haase, B., H. Signer-Hasler, M. M. Binns, G. Obexer-Ruff, R. Hauswirth, R. R. Bellone, D. Burger, S. Rieder, C. M. Wade, and T. Leeb. 2013. Accumulating mutations in series of haplotypes at the KIT and MITF loci are major determinants of white markings in Franches-Montagnes horses. PLoS One 8:e75071.
  8. Bai, R., A. Sen, Z. H. Yu, G. Yang, H. D. Wang, R. W. Fan, L. H. Lv, K-B. Lee, G. W. Smith, and C. S. Dong. 2010. Validation of methods for isolation and culture of alpaca melanocytes: A novel tool for in vitro studies of mechanisms controlling coat color. Asian Australas. J. Anim. Sci. 23:430-436.
  9. Dong, C. S., H. D. Wang, L. L. Xue, Y. J. Dong, L. Yang, R. W. Fan, X. J. Yu, X. Tian, S. H. Ma, and G. W. Smith. 2012. Coat color determination by miR-137 mediated down-regulation of microphthalmia-associated transcription factor in a mouse model. RNA 18:1679-1686.
  10. Ito, S. and K. Wakamatsu. 2003. Quantitative analysis of eumelanin and pheomelanin in humans, mice, and other animals: A comparative review. Pigment Cell Res. 16:523-531.
  11. Ito, S. and K. Wakamatsu. 2008. Chemistry of mixed melanogenesis-pivotal roles of dopaquinone. Photochem. Photobiol. 84:582-592.
  12. Jiang, Y. L., X. Z. Fan, Z. X. Lu, H. Tang, J. Q. Xu, and L. X. Du. 2002. Detection of $881^A{\rightarrow}881^G$ mutation in tyrosinase gene and associations with the black ear coat color in rabbits. Asian Australas J. Anim. Sci. 15:1395-1397.
  13. Lai, F. J., J. Ren, H. S. Ai, N. S. Ding, J. W. Ma, D. Q. Zeng, C. Y. Chen, Y. M. Guo, and L. S. Huang. 2007. Chinese white Rongchang pig does not have the dominant white allele of KIT but has the dominant black allele of MC1R. J. Hered. 98:84-87.
  14. Li, M. H., T. Tiirikka, and J. Kantanen. 2014. A genome-wide scan study identifies a single nucleotide substitution in ASIP associated with white versus non-white coat-colour variation in sheep (Ovis aries). Heredity 112:122-131.
  15. Livak, K. J. and T. D. Schmittgen. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the $2^{-{\Delta}{\Delta}C}T$ method. Methods 25:402-408.
  16. Ma, S. H., L. L. Xue, G. Xu, Y. Q. Hou, J. J. Geng, J. Cao, X. Y. He, H. D. Wang, and C. S. Dong. 2013. The influences of over-expressing miR-137 on TYRP-1 and TYRP-2 in melanocytes. China Agric. Sci. 46:3452-3459.
  17. Millar, S. E., M. W. Miller, M. E. Stevens, and G. S. Barsh. 1995. Expression and transgenic studies of the mouse agouti gene provide insight into the mechanisms by which mammalian coat color patterns are generated. Development 121:3223-3232.
  18. Ohta, S., Y. Imaizumi, Y. Okada, W. Akamatsu, R. Kuwahara, M. Ohyama, M. Amagai, Y. Matsuzake, S. Yamanaka, H. Okano, and Y. Kawakami. 2013. Generation of human melanocytes from induced pluripotent stem cells. PLoS ONE 6:e16182.
  19. Oldham, W. M. and H. E. Hamm. 2008. Heterotrimeric G protein activation by G-protein-coupled receptors. Nat. Rev. Mol. Cell Biol. 9:60-71.
  20. Perez-Oliva, A. B., C. Olivares, C. Jimenez-Cervantes, and J. C. Garcia-Borron. 2009. Mahogunin ring finger-1 (MGRN1) E3 ubiquitin ligase inhibits signaling from melanocortin receptor by competition with G alphas. J. Biol. Chem. 284:31714-31725.
  21. Robbins, L. S., J. H. Nadeau, K. R. Johnson, M. A. Kelly, L. Roselli-Rehfuss, E. Baack, K. G. Mountjoy, and R. D. Cone. 1993. Pigmentation phenotypes of variant extension locus alleles result from point mutations that alter MSH receptor function. Cell 72:827-834.
  22. Slominski, A., J. Wortsman, P. M. Plonka, K. U. Schallreuter, R. Paus, and D. J. Tobin. 2005. Hair follicle pigmentation. J. Invest. Dermatol. 124:13-21.
  23. Sturm, R. A., R. D. Teasdale, and N. F. Box. 2001. Human pigmentation genes: identification, structure and consequences of polymorphic variation. Gene 277:49-62.
  24. Tian, T. and W. X. Fan. 2006. Hair follicles signal transduction. Int. J. Derm. Venereol. 32:238-240.
  25. Tian, X., J. B. Jiang, R. W. Fan, H. D. Wang, X. L. Meng, X. Y. He, J. P. He, H. Q. Li, J. J. Geng, X. J. Yu, Y. F. Song, D. L. Zhang, J. B. Yao, G. W. Smith, and C. S. Dong. 2012. Identification and characterization of microRNAs in white and brown alpaca skin. BMC Genomics 13:555.
  26. Tian, X., X. L. Meng, L. Y. Wang, Y. F. Song, D. L. Zhang, Y. K. Ji, X. J. Li, and C. S. Dong. 2015. Molecular cloning, mRNA expression and tissue distribution analysis of Slc7a11 gene in alpaca (Lama paco) skins associated with different coat colours. Gene 555:88-94.
  27. Vage, D. I., M. Nieminen, D. G. Anderson, and K. H. Roed. 2014. Two missense mutations in melanocortin 1 receptor (MC1R) are strongly associated with dark ventral coat color in reindeer (Rangifer tarandus). Anim. Genet. 45:750-753.
  28. Van Raamsdonk, C. D., G. S. Barsh, K. Wakamatsu, and S. Ito. 2009. Independent regulation of hair and skin color by two G protein-coupled pathways. Pigment Cell Melanoma Res. 22:819-826.
  29. Van Raamsdonk, C. D., K. R. Fitch, H. Fuchs, M. H. de Angelis, and G. S Barsh. 2004. Effects of G-protein mutations on skin color. Nat. Genet. 36:961-968.
  30. Yu, X. J., X. Y. He, J. B. Jiang, J. P. He, R. W. Fan, H. D. Wang, J. J. Geng, and C. S. Dong. 2015. Expression and tissue distribution of hepatocyte growth factor (HGF) and its receptor (c-Met) in alpacas (Vicugna pacos) skins associated with white and brown coat colors. Acta Histochem. 117:624-628.