Abstract
The pupoid fetus (pf) and repeated epilation (Er) mutations of mice result in a failure of epidermal differentiation in homozygotes. Expression of the epidermal keratins has been followed in pf/pf and Er/Er mice by two-dimensional gel electrophoresis, and by immunohistochemistry and Western blotting using polyclonal antibodies that are monospecific for individual keratin polypeptides. Our results show that expression of the differentiation-specific keratins (K1 and K10) is delayed in both the pf/pf and Er/Er mutants and that, when these keratins do appear later in development, they are localized in the deeper layers of the thickened mutant epidermis. Conversely, K6 and K16, two keratins found in low abundance in normal epidermis, are abundant in mutant epidermis. In newborn mutant epidermis, K6 and K16 are found to be most abundant in the outermost epidermal cells, a distribution opposite to that of K1 and K10. These findings suggest that the expression of these hyperplastic keratins in mutant mice may occur to the exclusion of the differentiation-specific keratins both during development and in newborn animals. Differentiation, and an apparently normal pattern of keratin expression, occur when whole pf/pf or Er/Er skin is grafted to normal mice. These results suggest that the pf and Er genes may be expressed systemically and that transfer of the mutant skin to a "normal" environment results in the recovery of a normal phenotype.
Full Text
The Full Text of this article is available as a PDF (5.2 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Anderson S., Ede D. A. The behaviour in vitro of epidermal cells from normal and pupoid foetus mutant mouse embryos. J Cell Sci. 1985 Nov;79:305–315. doi: 10.1242/jcs.79.1.305. [DOI] [PubMed] [Google Scholar]
- Anderson S., Ede D. A., Watson P. J. Embryonic development of the mouse mutant pupoid foetus (pf/pf). Anat Embryol (Berl) 1985;172(1):115–122. doi: 10.1007/BF00318950. [DOI] [PubMed] [Google Scholar]
- Banks-Schlegel S. P. Keratin alterations during embryonic epidermal differentiation: a presage of adult epidermal maturation. J Cell Biol. 1982 Jun;93(3):551–559. doi: 10.1083/jcb.93.3.551. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bowden P. E., Quinlan R. A., Breitkreutz D., Fusenig N. E. Proteolytic modification of acidic and basic keratins during terminal differentiation of mouse and human epidermis. Eur J Biochem. 1984 Jul 2;142(1):29–36. doi: 10.1111/j.1432-1033.1984.tb08246.x. [DOI] [PubMed] [Google Scholar]
- Breitkreutz D., Bohnert A., Herzmann E., Bowden P. E., Boukamp P., Fusenig N. E. Differentiation specific functions in cultured and transplanted mouse keratinocytes: environmental influences on ultrastructure and keratin expression. Differentiation. 1984;26(2):154–169. doi: 10.1111/j.1432-0436.1984.tb01389.x. [DOI] [PubMed] [Google Scholar]
- Dale B. A., Holbrook K. A., Kimball J. R., Hoff M., Sun T. T. Expression of epidermal keratins and filaggrin during human fetal skin development. J Cell Biol. 1985 Oct;101(4):1257–1269. doi: 10.1083/jcb.101.4.1257. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Doran T. I., Vidrich A., Sun T. T. Intrinsic and extrinsic regulation of the differentiation of skin, corneal and esophageal epithelial cells. Cell. 1980 Nov;22(1 Pt 1):17–25. doi: 10.1016/0092-8674(80)90150-6. [DOI] [PubMed] [Google Scholar]
- Fisher C. Abnormal development in the skin of the pupoid fetus (pf/pf) mutant mouse: abnormal keratinization, recovery of a normal phenotype, and relationship to the repeated epilation (Er/Er) mutant mouse. Curr Top Dev Biol. 1987;22:209–234. doi: 10.1016/s0070-2153(08)60105-2. [DOI] [PubMed] [Google Scholar]
- Fisher C., Dale B. A., Kollar E. J. Abnormal keratinization in the pupoid fetus (pf/pf) mutant mouse epidermis. Dev Biol. 1984 Apr;102(2):290–299. doi: 10.1016/0012-1606(84)90194-5. [DOI] [PubMed] [Google Scholar]
- Fisher C., Holbrook K. A. Cell surface and cytoskeletal changes associated with epidermal stratification and differentiation in organ cultures of embryonic human skin. Dev Biol. 1987 Jan;119(1):231–241. doi: 10.1016/0012-1606(87)90224-7. [DOI] [PubMed] [Google Scholar]
- Fisher C., Kollar E. J. Abnormal skin development in pupoid foetus (pf/pf) mutant mice. J Embryol Exp Morphol. 1985 Jun;87:47–64. [PubMed] [Google Scholar]
- Franke W. W., Schiller D. L., Moll R., Winter S., Schmid E., Engelbrecht I., Denk H., Krepler R., Platzer B. Diversity of cytokeratins. Differentiation specific expression of cytokeratin polypeptides in epithelial cells and tissues. J Mol Biol. 1981 Dec 25;153(4):933–959. doi: 10.1016/0022-2836(81)90460-5. [DOI] [PubMed] [Google Scholar]
- Fuchs E., Green H. Changes in keratin gene expression during terminal differentiation of the keratinocyte. Cell. 1980 Apr;19(4):1033–1042. doi: 10.1016/0092-8674(80)90094-x. [DOI] [PubMed] [Google Scholar]
- Guenet J. L., Salzgeber B., Tassin M. T. Repeated epilation: a genetic epidermal syndrome in mice. J Hered. 1979 Mar-Apr;70(2):90–94. doi: 10.1093/oxfordjournals.jhered.a109223. [DOI] [PubMed] [Google Scholar]
- Harding C. R., Scott I. R. Histidine-rich proteins (filaggrins): structural and functional heterogeneity during epidermal differentiation. J Mol Biol. 1983 Nov 5;170(3):651–673. doi: 10.1016/s0022-2836(83)80126-0. [DOI] [PubMed] [Google Scholar]
- Hennings H., Michael D., Cheng C., Steinert P., Holbrook K., Yuspa S. H. Calcium regulation of growth and differentiation of mouse epidermal cells in culture. Cell. 1980 Jan;19(1):245–254. doi: 10.1016/0092-8674(80)90406-7. [DOI] [PubMed] [Google Scholar]
- Holbrook K. A., Dale B. A., Brown K. S. Abnormal epidermal keratinization in the repeated epilation mutant mouse. J Cell Biol. 1982 Feb;92(2):387–397. doi: 10.1083/jcb.92.2.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
- Huang F. L., Roop D. R., De Luca L. M. Vitamin A deficiency and keratin biosynthesis in cultured hamster trachea. In Vitro Cell Dev Biol. 1986 Apr;22(4):223–230. doi: 10.1007/BF02623307. [DOI] [PubMed] [Google Scholar]
- Knapp B., Rentrop M., Schweizer J., Winter H. Three cDNA sequences of mouse type I keratins. Cellular localization of the mRNAs in normal and hyperproliferative tissues. J Biol Chem. 1987 Jan 15;262(2):938–945. [PubMed] [Google Scholar]
- LUFT J. H. Improvements in epoxy resin embedding methods. J Biophys Biochem Cytol. 1961 Feb;9:409–414. doi: 10.1083/jcb.9.2.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Moll R., Moll I., Wiest W. Changes in the pattern of cytokeratin polypeptides in epidermis and hair follicles during skin development in human fetuses. Differentiation. 1982;23(2):170–178. doi: 10.1111/j.1432-0436.1982.tb01280.x. [DOI] [PubMed] [Google Scholar]
- O'Farrell P. Z., Goodman H. M., O'Farrell P. H. High resolution two-dimensional electrophoresis of basic as well as acidic proteins. Cell. 1977 Dec;12(4):1133–1141. doi: 10.1016/0092-8674(77)90176-3. [DOI] [PubMed] [Google Scholar]
- Ouellet T., Lussier M., Bélanger C., Kessous A., Royal A. Differential expression of keratin genes during mouse development. Dev Biol. 1986 Feb;113(2):282–287. doi: 10.1016/0012-1606(86)90163-6. [DOI] [PubMed] [Google Scholar]
- RICHARDSON K. C., JARETT L., FINKE E. H. Embedding in epoxy resins for ultrathin sectioning in electron microscopy. Stain Technol. 1960 Nov;35:313–323. doi: 10.3109/10520296009114754. [DOI] [PubMed] [Google Scholar]
- Roop D. R., Cheng C. K., Titterington L., Meyers C. A., Stanley J. R., Steinert P. M., Yuspa S. H. Synthetic peptides corresponding to keratin subunits elicit highly specific antibodies. J Biol Chem. 1984 Jul 10;259(13):8037–8040. [PubMed] [Google Scholar]
- Roop D. R., Cheng C. K., Toftgard R., Stanley J. R., Steinert P. M., Yuspa S. H. The use of cDNA clones and monospecific antibodies as probes to monitor keratin gene expression. Ann N Y Acad Sci. 1985;455:426–435. doi: 10.1111/j.1749-6632.1985.tb50426.x. [DOI] [PubMed] [Google Scholar]
- Roop D. R., Hawley-Nelson P., Cheng C. K., Yuspa S. H. Keratin gene expression in mouse epidermis and cultured epidermal cells. Proc Natl Acad Sci U S A. 1983 Feb;80(3):716–720. doi: 10.1073/pnas.80.3.716. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Salaün J., Salzgeber B., Guénet J. L. The differentiation of repeated epilation (Er/Er) mouse mutant skin in organ culture and in grafts. Anat Embryol (Berl) 1986;174(2):195–205. doi: 10.1007/BF00824335. [DOI] [PubMed] [Google Scholar]
- Salzgeber B., Guénet J. L. Studies on "Repeated Epilation" mouse mutant embryos: II. Development of limb, tail, and skin defects. J Craniofac Genet Dev Biol. 1984;4(2):95–114. [PubMed] [Google Scholar]
- Schermer A., Galvin S., Sun T. T. Differentiation-related expression of a major 64K corneal keratin in vivo and in culture suggests limbal location of corneal epithelial stem cells. J Cell Biol. 1986 Jul;103(1):49–62. doi: 10.1083/jcb.103.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schweizer J., Kinjo M., Fürstenberger G., Winter H. Sequential expression of mRNA-encoded keratin sets in neonatal mouse epidermis: basal cells with properties of terminally differentiating cells. Cell. 1984 May;37(1):159–170. doi: 10.1016/0092-8674(84)90311-8. [DOI] [PubMed] [Google Scholar]
- Schweizer J., Winter H. Keratin biosynthesis in normal mouse epithelia and in squamous cell carcinomas. mRNA-dependent alterations of the primary structure of distinct keratin subunits in tumors. J Biol Chem. 1983 Nov 10;258(21):13268–13272. [PubMed] [Google Scholar]
- Schweizer J., Winter H. Keratin polypeptide analysis in fetal and in terminally differentiating newborn mouse epidermis. Differentiation. 1982;22(1):19–24. doi: 10.1111/j.1432-0436.1982.tb01219.x. [DOI] [PubMed] [Google Scholar]
- Steinert P. M., Steven A. C., Roop D. R. The molecular biology of intermediate filaments. Cell. 1985 Sep;42(2):411–420. doi: 10.1016/0092-8674(85)90098-4. [DOI] [PubMed] [Google Scholar]
- Tassin M. T., Salzgeber B., Guenet J. L. Studies on "repeated epilation" mouse mutant embryos: I. Development of facial malformations. J Craniofac Genet Dev Biol. 1983;3(3):289–307. [PubMed] [Google Scholar]
- Tseng S. C., Jarvinen M. J., Nelson W. G., Huang J. W., Woodcock-Mitchell J., Sun T. T. Correlation of specific keratins with different types of epithelial differentiation: monoclonal antibody studies. Cell. 1982 Sep;30(2):361–372. doi: 10.1016/0092-8674(82)90234-3. [DOI] [PubMed] [Google Scholar]
- Weiss R. A., Eichner R., Sun T. T. Monoclonal antibody analysis of keratin expression in epidermal diseases: a 48- and 56-kdalton keratin as molecular markers for hyperproliferative keratinocytes. J Cell Biol. 1984 Apr;98(4):1397–1406. doi: 10.1083/jcb.98.4.1397. [DOI] [PMC free article] [PubMed] [Google Scholar]