Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Nov 1;90(21):10270–10274. doi: 10.1073/pnas.90.21.10270

Tissue- and stratum-specific expression of the human involucrin promoter in transgenic mice.

J M Carroll 1, K M Albers 1, J A Garlick 1, R Harrington 1, L B Taichman 1
PMCID: PMC47756  PMID: 8234288

Abstract

Involucrin is a marker of keratinocyte terminal differentiation and is expressed only in the suprabasal layers of stratified squamous epithelium. In a previous study with various cell types in culture, we noted that expression of the putative human involucrin promoter was keratinocyte specific. To determine if this promoter is sufficient to direct expression to the suprabasal cells of stratified squamous epithelia in vivo, we have now generated transgenic mouse lines harboring the involucrin promoter sequences linked to a beta-galactosidase reporter gene. In the resulting lines, beta-galactosidase was expressed in the suprabasal compartment of stratified squamous epithelia and in hair follicles in a tissue-specific manner. In the palate, distinct vertical stacks of beta-galactosidase-expressing cells were present, suggesting movement of clonally derived cells through the epithelium. The involucrin gene has a single intron upstream of the translational start site, and removal of this intron did not affect tissue- or stratum-specific expression. These results show that the 3.7-kb involucrin upstream sequences contain all the information necessary for a high level of tissue- and stratum-specific expression.

Full text

PDF
10273

Images in this article

Selected References

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

  1. Asselineau D., Bernard B. A., Bailly C., Darmon M. Retinoic acid improves epidermal morphogenesis. Dev Biol. 1989 Jun;133(2):322–335. doi: 10.1016/0012-1606(89)90037-7. [DOI] [PubMed] [Google Scholar]
  2. Bailleul B., Surani M. A., White S., Barton S. C., Brown K., Blessing M., Jorcano J., Balmain A. Skin hyperkeratosis and papilloma formation in transgenic mice expressing a ras oncogene from a suprabasal keratin promoter. Cell. 1990 Aug 24;62(4):697–708. doi: 10.1016/0092-8674(90)90115-u. [DOI] [PubMed] [Google Scholar]
  3. Banks-Schlegel S., Green H. Involucrin synthesis and tissue assembly by keratinocytes in natural and cultured human epithelia. J Cell Biol. 1981 Sep;90(3):732–737. doi: 10.1083/jcb.90.3.732. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bernard B. A., Reano A., Darmon Y. M., Thivolet J. Precocious appearance of involucrin and epidermal transglutaminase during differentiation of psoriatic skin. Br J Dermatol. 1986 Mar;114(3):279–283. doi: 10.1111/j.1365-2133.1986.tb02818.x. [DOI] [PubMed] [Google Scholar]
  5. Bernerd F., Magnaldo T., Darmon M. Delayed onset of epidermal differentiation in psoriasis. J Invest Dermatol. 1992 Jun;98(6):902–910. doi: 10.1111/1523-1747.ep12460344. [DOI] [PubMed] [Google Scholar]
  6. Byrne C., Fuchs E. Probing keratinocyte and differentiation specificity of the human K5 promoter in vitro and in transgenic mice. Mol Cell Biol. 1993 Jun;13(6):3176–3190. doi: 10.1128/mcb.13.6.3176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Carroll J. M., Taichman L. B. Characterization of the human involucrin promoter using a transient beta-galactosidase assay. J Cell Sci. 1992 Dec;103(Pt 4):925–930. doi: 10.1242/jcs.103.4.925. [DOI] [PubMed] [Google Scholar]
  8. Coulombe P. A., Hutton M. E., Vassar R., Fuchs E. A function for keratins and a common thread among different types of epidermolysis bullosa simplex diseases. J Cell Biol. 1991 Dec;115(6):1661–1674. doi: 10.1083/jcb.115.6.1661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Crish J. F., Howard J. M., Zaim T. M., Murthy S., Eckert R. L. Tissue-specific and differentiation-appropriate expression of the human involucrin gene in transgenic mice: an abnormal epidermal phenotype. Differentiation. 1993 Jul;53(3):191–200. doi: 10.1111/j.1432-0436.1993.tb00708.x. [DOI] [PubMed] [Google Scholar]
  10. Eckert R. L., Green H. Structure and evolution of the human involucrin gene. Cell. 1986 Aug 15;46(4):583–589. doi: 10.1016/0092-8674(86)90884-6. [DOI] [PubMed] [Google Scholar]
  11. Fuchs E. Epidermal differentiation. Curr Opin Cell Biol. 1990 Dec;2(6):1028–1035. doi: 10.1016/0955-0674(90)90152-5. [DOI] [PubMed] [Google Scholar]
  12. Fuchs E., Green H. Regulation of terminal differentiation of cultured human keratinocytes by vitamin A. Cell. 1981 Sep;25(3):617–625. doi: 10.1016/0092-8674(81)90169-0. [DOI] [PubMed] [Google Scholar]
  13. Green H., Djian P. Consecutive actions of different gene-altering mechanisms in the evolution of involucrin. Mol Biol Evol. 1992 Nov;9(6):977–1017. doi: 10.1093/oxfordjournals.molbev.a040775. [DOI] [PubMed] [Google Scholar]
  14. Haftek M., Serre G., Mils V., Thivolet J. Immunocytochemical evidence for a possible role of cross-linked keratinocyte envelopes in stratum corneum cohesion. J Histochem Cytochem. 1991 Nov;39(11):1531–1538. doi: 10.1177/39.11.1717544. [DOI] [PubMed] [Google Scholar]
  15. Hashimoto T., Inamoto N., Nakamura K., Harada R. Involucrin expression in skin appendage tumours. Br J Dermatol. 1987 Sep;117(3):325–332. doi: 10.1111/j.1365-2133.1987.tb04139.x. [DOI] [PubMed] [Google Scholar]
  16. Hohl D. Cornified cell envelope. Dermatologica. 1990;180(4):201–211. doi: 10.1159/000248031. [DOI] [PubMed] [Google Scholar]
  17. Kopan R., Traska G., Fuchs E. Retinoids as important regulators of terminal differentiation: examining keratin expression in individual epidermal cells at various stages of keratinization. J Cell Biol. 1987 Jul;105(1):427–440. doi: 10.1083/jcb.105.1.427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kozak M. An analysis of vertebrate mRNA sequences: intimations of translational control. J Cell Biol. 1991 Nov;115(4):887–903. doi: 10.1083/jcb.115.4.887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Leask A., Byrne C., Fuchs E. Transcription factor AP2 and its role in epidermal-specific gene expression. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):7948–7952. doi: 10.1073/pnas.88.18.7948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lee S. C., Wang M., McBride O. W., O'Keefe E. J., Kim I. G., Steinert P. M. Human trichohyalin gene is clustered with the genes for other epidermal structural proteins and calcium-binding proteins at chromosomal locus 1q21. J Invest Dermatol. 1993 Jan;100(1):65–68. doi: 10.1111/1523-1747.ep12354504. [DOI] [PubMed] [Google Scholar]
  21. Mackenzie J. C. Ordered structure of the stratum corneum of mammalian skin. Nature. 1969 May 31;222(5196):881–882. doi: 10.1038/222881a0. [DOI] [PubMed] [Google Scholar]
  22. Magnaldo T., Bernerd F., Asselineau D., Darmon M. Expression of loricrin is negatively controlled by retinoic acid in human epidermis reconstructed in vitro. Differentiation. 1992 Jan;49(1):39–46. doi: 10.1111/j.1432-0436.1992.tb00767.x. [DOI] [PubMed] [Google Scholar]
  23. Maniatis T., Fritsch E. F., Lauer J., Lawn R. M. The molecular genetics of human hemoglobins. Annu Rev Genet. 1980;14:145–178. doi: 10.1146/annurev.ge.14.120180.001045. [DOI] [PubMed] [Google Scholar]
  24. Mansbridge J. N., Knapp A. M. Changes in keratinocyte maturation during wound healing. J Invest Dermatol. 1987 Sep;89(3):253–263. doi: 10.1111/1523-1747.ep12471216. [DOI] [PubMed] [Google Scholar]
  25. McKinley-Grant L. J., Idler W. W., Bernstein I. A., Parry D. A., Cannizzaro L., Croce C. M., Huebner K., Lessin S. R., Steinert P. M. Characterization of a cDNA clone encoding human filaggrin and localization of the gene to chromosome region 1q21. Proc Natl Acad Sci U S A. 1989 Jul;86(13):4848–4852. doi: 10.1073/pnas.86.13.4848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mehrel T., Hohl D., Rothnagel J. A., Longley M. A., Bundman D., Cheng C., Lichti U., Bisher M. E., Steven A. C., Steinert P. M. Identification of a major keratinocyte cell envelope protein, loricrin. Cell. 1990 Jun 15;61(6):1103–1112. doi: 10.1016/0092-8674(90)90073-n. [DOI] [PubMed] [Google Scholar]
  27. Moll R., Franke W. W., Schiller D. L., Geiger B., Krepler R. The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell. 1982 Nov;31(1):11–24. doi: 10.1016/0092-8674(82)90400-7. [DOI] [PubMed] [Google Scholar]
  28. Oshima R. G., Abrams L., Kulesh D. Activation of an intron enhancer within the keratin 18 gene by expression of c-fos and c-jun in undifferentiated F9 embryonal carcinoma cells. Genes Dev. 1990 May;4(5):835–848. doi: 10.1101/gad.4.5.835. [DOI] [PubMed] [Google Scholar]
  29. Potten C. S. Cell replacement in epidermis (keratopoiesis) via discrete units of proliferation. Int Rev Cytol. 1981;69:271–318. doi: 10.1016/s0074-7696(08)62326-8. [DOI] [PubMed] [Google Scholar]
  30. Rice R. H., Green H. Presence in human epidermal cells of a soluble protein precursor of the cross-linked envelope: activation of the cross-linking by calcium ions. Cell. 1979 Nov;18(3):681–694. doi: 10.1016/0092-8674(79)90123-5. [DOI] [PubMed] [Google Scholar]
  31. Rosenthal D. S., Griffiths C. E., Yuspa S. H., Roop D. R., Voorhees J. J. Acute or chronic topical retinoic acid treatment of human skin in vivo alters the expression of epidermal transglutaminase, loricrin, involucrin, filaggrin, and keratins 6 and 13 but not keratins 1, 10, and 14. J Invest Dermatol. 1992 Mar;98(3):343–350. doi: 10.1111/1523-1747.ep12499802. [DOI] [PubMed] [Google Scholar]
  32. Rosenthal D. S., Steinert P. M., Chung S., Huff C. A., Johnson J., Yuspa S. H., Roop D. R. A human epidermal differentiation-specific keratin gene is regulated by calcium but not negative modulators of differentiation in transgenic mouse keratinocytes. Cell Growth Differ. 1991 Feb;2(2):107–113. [PubMed] [Google Scholar]
  33. Simon M., Phillips M., Green H., Stroh H., Glatt K., Burns G., Latt S. A. Absence of a single repeat from the coding region of the human involucrin gene leading to RFLP. Am J Hum Genet. 1989 Dec;45(6):910–916. [PMC free article] [PubMed] [Google Scholar]
  34. Takahashi H., Iizuka H. Analysis of the 5'-upstream promoter region of human involucrin gene: activation by 12-O-tetradecanoylphorbol-13-acetate. J Invest Dermatol. 1993 Jan;100(1):10–15. doi: 10.1111/1523-1747.ep12349867. [DOI] [PubMed] [Google Scholar]
  35. Vassar R., Rosenberg M., Ross S., Tyner A., Fuchs E. Tissue-specific and differentiation-specific expression of a human K14 keratin gene in transgenic mice. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1563–1567. doi: 10.1073/pnas.86.5.1563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Watt F. M., Green H. Involucrin synthesis is correlated with cell size in human epidermal cultures. J Cell Biol. 1981 Sep;90(3):738–742. doi: 10.1083/jcb.90.3.738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Watt F. M., Green H. Stratification and terminal differentiation of cultured epidermal cells. Nature. 1982 Feb 4;295(5848):434–436. doi: 10.1038/295434a0. [DOI] [PubMed] [Google Scholar]
  38. Watt F. M. Terminal differentiation of epidermal keratinocytes. Curr Opin Cell Biol. 1989 Dec;1(6):1107–1115. doi: 10.1016/s0955-0674(89)80058-4. [DOI] [PubMed] [Google Scholar]
  39. Yaffe M. B., Murthy S., Eckert R. L. Evidence that involucrin is a covalently linked constituent of highly purified cultured keratinocyte cornified envelopes. J Invest Dermatol. 1993 Jan;100(1):3–9. doi: 10.1111/1523-1747.ep12349857. [DOI] [PubMed] [Google Scholar]
  40. Yoneda K., Hohl D., McBride O. W., Wang M., Cehrs K. U., Idler W. W., Steinert P. M. The human loricrin gene. J Biol Chem. 1992 Sep 5;267(25):18060–18066. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES