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. 1994 Jun 7;91(12):5667–5671. doi: 10.1073/pnas.91.12.5667

Differences in dorsal and ventral pigmentation result from regional expression of the mouse agouti gene.

H Vrieling 1, D M Duhl 1, S E Millar 1, K A Miller 1, G S Barsh 1
PMCID: PMC44057  PMID: 8202545

Abstract

The agouti coat color gene encodes a paracrine signaling molecule that controls the production of yellow and black pigment by melanocytes within hair follicles. Some agouti alleles affect the dorsum and ventrum independently, which has provided the basis for speculation that agouti gene action in different regions of the body is controlled by distinct genetic loci that are closely linked. Using a combination of cDNA cloning and RNA expression studies, we find that alternative isoforms of agouti mRNA contain different noncoding first exons located 100 kb apart, whose patterns of expression indicate independent control by regulatory elements that are either ventral specific or hair cycle specific. These results demonstrate that the apparent genetic complexity of the agouti locus is explained by the existence of multiple regulatory elements exerting control over a single coding sequence and provide a conceptual basis for understanding differences in dorsal and ventral hair coloration in many mammalian species. The ventral-specific agouti isoform represents an example of a transcript whose expression is restricted to ventral skin and provide an approach to investigate the mechanisms by which dorsal-ventral differences in gene expression are established and maintained.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barsh G. S., Epstein C. J. Physical and genetic characterization of a 75-kilobase deletion associated with al, a recessive lethal allele at the mouse agouti locus. Genetics. 1989 Apr;121(4):811–818. doi: 10.1093/genetics/121.4.811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bultman S. J., Michaud E. J., Woychik R. P. Molecular characterization of the mouse agouti locus. Cell. 1992 Dec 24;71(7):1195–1204. doi: 10.1016/s0092-8674(05)80067-4. [DOI] [PubMed] [Google Scholar]
  3. Dickie M. M. Mutations at the agouti locus in the mouse. J Hered. 1969 Jan-Feb;60(1):20–25. doi: 10.1093/oxfordjournals.jhered.a107920. [DOI] [PubMed] [Google Scholar]
  4. Fukuzawa T., Ide H. A ventrally localized inhibitor of melanization in Xenopus laevis skin. Dev Biol. 1988 Sep;129(1):25–36. doi: 10.1016/0012-1606(88)90158-3. [DOI] [PubMed] [Google Scholar]
  5. GALBRAITH D. B. THE AGOUTI PIGMENT PATTERN OF THE MOUSE: A QUANTITATIVE AND EXPERIMENTAL STUDY. J Exp Zool. 1964 Feb;155:71–90. doi: 10.1002/jez.1401550106. [DOI] [PubMed] [Google Scholar]
  6. Jones C. M., Lyons K. M., Hogan B. L. Expression of TGF-beta-related genes during mouse embryo whisker morphogenesis. Ann N Y Acad Sci. 1991 Dec 26;642:339–345. doi: 10.1111/j.1749-6632.1991.tb24399.x. [DOI] [PubMed] [Google Scholar]
  7. Kawabe T. T., Rea T. J., Flenniken A. M., Williams B. R., Groppi V. E., Buhl A. E. Localization of TIMP in cycling mouse hair. Development. 1991 Apr;111(4):877–879. doi: 10.1242/dev.111.4.877. [DOI] [PubMed] [Google Scholar]
  8. Kreutzfeld K. L., Fukuzawa T., Bagnara J. T. Effects of a ventrally localized inhibitor of melanization on cultured S91 and B16 mouse melanoma. Pigment Cell Res. 1989 Mar-Apr;2(2):123–125. doi: 10.1111/j.1600-0749.1989.tb00172.x. [DOI] [PubMed] [Google Scholar]
  9. Lyon M. F., Fisher G., Glenister P. H. A recessive allele of the mouse agouti locus showing lethality with yellow, Ay. Genet Res. 1985 Aug;46(1):95–99. doi: 10.1017/s0016672300022485. [DOI] [PubMed] [Google Scholar]
  10. MacCabe J. A., Errick J., Saunders J. W., Jr Ectodermal control of the dorsoventral axis in the leg bud of the chick embryo. Dev Biol. 1974 Jul;39(1):69–82. doi: 10.1016/s0012-1606(74)80009-6. [DOI] [PubMed] [Google Scholar]
  11. Michaud E. J., Bultman S. J., Stubbs L. J., Woychik R. P. The embryonic lethality of homozygous lethal yellow mice (Ay/Ay) is associated with the disruption of a novel RNA-binding protein. Genes Dev. 1993 Jul;7(7A):1203–1213. doi: 10.1101/gad.7.7a.1203. [DOI] [PubMed] [Google Scholar]
  12. Miller M. W., Duhl D. M., Vrieling H., Cordes S. P., Ollmann M. M., Winkes B. M., Barsh G. S. Cloning of the mouse agouti gene predicts a secreted protein ubiquitously expressed in mice carrying the lethal yellow mutation. Genes Dev. 1993 Mar;7(3):454–467. doi: 10.1101/gad.7.3.454. [DOI] [PubMed] [Google Scholar]
  13. Padgett R. A., Grabowski P. J., Konarska M. M., Seiler S., Sharp P. A. Splicing of messenger RNA precursors. Annu Rev Biochem. 1986;55:1119–1150. doi: 10.1146/annurev.bi.55.070186.005351. [DOI] [PubMed] [Google Scholar]
  14. Parr B. A., Shea M. J., Vassileva G., McMahon A. P. Mouse Wnt genes exhibit discrete domains of expression in the early embryonic CNS and limb buds. Development. 1993 Sep;119(1):247–261. doi: 10.1242/dev.119.1.247. [DOI] [PubMed] [Google Scholar]
  15. Pincus G. A SPONTANEOUS MUTATION IN THE HOUSE MOUSE. Proc Natl Acad Sci U S A. 1929 Feb 15;15(2):85–88. doi: 10.1073/pnas.15.2.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Poole T. W., Silvers W. K. The development of regional pigmentation patterns in black and tan (at) mice. J Exp Zool. 1976 Jul;197(1):115–119. doi: 10.1002/jez.1401970113. [DOI] [PubMed] [Google Scholar]
  17. Russell E S. A Quantitative Histological Study of the Pigment Found in the Coat-Color Mutants of the House Mouse. IV. the Nature of the Effects of Genic Substitution in Five Major Allelic Series. Genetics. 1949 Mar;34(2):146–166. doi: 10.1093/genetics/34.2.146. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. SILVERS W. K. An experimental approach to action of genes at the agouti locus in the mouse. II. Transplants of newborn aa ventral skin to ata, Awa and aa hosts. J Exp Zool. 1958 Feb;137(1):181–187. doi: 10.1002/jez.1401370109. [DOI] [PubMed] [Google Scholar]
  19. SILVERS W. K. An experimental approach to action of genes at the agouti locus in the mouse. III. Transplants of newborn Aw-, A-and at-skin to Ay-, Aw-, A-and aa hosts. J Exp Zool. 1958 Feb;137(1):189–196. doi: 10.1002/jez.1401370110. [DOI] [PubMed] [Google Scholar]
  20. Siracusa L. D., Russell L. B., Eicher E. M., Corrow D. J., Copeland N. G., Jenkins N. A. Genetic organization of the agouti region of the mouse. Genetics. 1987 Sep;117(1):93–100. doi: 10.1093/genetics/117.1.93. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Slominski A., Paus R., Mazurkiewicz J. Proopiomelanocortin expression in the skin during induced hair growth in mice. Experientia. 1992 Jan 15;48(1):50–54. doi: 10.1007/BF01923606. [DOI] [PubMed] [Google Scholar]
  22. Tam P. P., Beddington R. S. The formation of mesodermal tissues in the mouse embryo during gastrulation and early organogenesis. Development. 1987 Jan;99(1):109–126. doi: 10.1242/dev.99.1.109. [DOI] [PubMed] [Google Scholar]
  23. Wallace W. E. Pseudoallelism at the agouti locus in the mouse. J Hered. 1965 Nov-Dec;56(6):267–271. doi: 10.1093/oxfordjournals.jhered.a107436. [DOI] [PubMed] [Google Scholar]

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