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Gene Review

Krt14  -  keratin 14

Mus musculus

Synonyms: AI626930, CK-14, Cytokeratin 14, Cytokeratin-14, K14, ...
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Disease relevance of Krt14

  • Absence of K14 gives rise to epidermolysis bullosa simplex, a human blistering skin disorder involving cytolysis in the basal layer of epidermis [1].
  • These results suggest that papilloma cells fail to respond to or generate signals to regulate K14 expression in the differentiating suprabasal cell layers and may not fully express their suprabasal cell keratins [2].
  • K14 protein and transcripts are highly expressed in all strata in carcinomas while protein and transcripts for K1 and K10 are essentially absent [2].
  • The replacement of PTHrP expression in the enamel epithelium with a keratin 14-driven transgene corrects the defect in bone resorption and restores the normal program of tooth eruption [3].
  • K14-MEK mice exhibit moderate hyperplasia, with spontaneous skin tumor development within 5 weeks of birth [4].

Psychiatry related information on Krt14


High impact information on Krt14

  • The expression of beta1 integrin, which is preferentially expressed in epidermal stem cells is unusually low in the epidermis of K14.MYC2 mice [6].
  • Adult K14.MYC2 mice gradually lose their hair and develop spontaneous ulcerated lesions due to a severe impairment in wound healing; their keratinocytes show impaired migration in response to wounding [6].
  • Label-retaining analysis to identify epidermal stem cells reveals a 75% reduction in the number of stem cells in 3-month-old K14.MYC2 mice, compared with wildtype mice [6].
  • To determine the role of c-Myc in epidermal stem cells in vivo, we have targeted expression of human MYC2 to the hair follicles and the basal layer of mouse epidermis using a keratin 14 vector (K14.MYC2) [6].
  • We now demonstrate that two patients with spontaneous cases of Dowling-Meara EBS have point mutations in a critical region in one (K14) of two basal keratin genes [7].

Chemical compound and disease context of Krt14

  • This lymphoproliferative skin disease is substantially more severe in mice homozygous for the K14/IL-7 transgene [8].
  • Interestingly, similar features of carcinogenesis, including multiple, large (up to 0.5 cm) exophytic papillary squamous tumors and invasive squamous cell carcinomas, increased bromodeoxyuridine staining, and increased K14 expression, were also observed in the esophagi of 4-NQO-treated mice [9].
  • To create targeted somatic mutations in the epidermis, we established transgenic mice expressing the bacteriophage P1 Cre recombinase or the tamoxifen-dependent Cre-ER(T2) recombinase under the control of the human keratin 14 (K14) promoter [10].

Biological context of Krt14

  • The functional diversity of epidermal keratins revealed by the partial rescue of the keratin 14 null phenotype by keratin 16 [11].
  • When combinations of active recombinant gene constructs for keratins 1, 5, 10, and 14 were tested in transient NIH 3T3 transfections, the most intact cytokeratin network observed by immunofluorescence was formed by the K5/K14 pair [12].
  • To model human papillomavirus-induced neoplastic progression, expression of the early region of human papillomavirus type 16 (HPV16) was targeted to the basal cells of the squamous epithelium in transgenic mice, using a human keratin 14 (K14) enhancer/promoter [13].
  • K14 null animals die several days after birth, making the detailed study of the consequences of K14 deletion in epidermal cell physiology in vivo particularly difficult [14].
  • Keratin 14 (K14) is believed to play a pivotal role in the maintenance of epidermal cell shape and contributing to their resistance to mechanical trauma, thereby protecting the cells from lysing [14].

Anatomical context of Krt14

  • While a structural function has been clearly defined for K14, we have proposed that a function of K16 may be to play a role in the process of keratinocyte activation that occurs after acute injury to stratified epithelia [11].
  • Several keratinocyte cell lines were generated from 6-day-old mice homozygous for a targeted disruption of the K14 gene (lines designated MKC-5, MKC-23, and MKC-33) and from their wild-type littermates (lines designated MKC-1 and MKC-6) [14].
  • Keratin 14 protein in cultured nonparenchymal rat hepatic epithelial cells: characterization of keratin 14 and keratin 19 as antigens for the commonly used mouse monoclonal antibody OV-6 [15].
  • In the study presented here, we confirmed by protein sequence analysis that K14 was a major component of the intermediate filaments in a nonparenchymal cell line of hepatic origin [15].
  • Immunocytochemical analysis of the cells in monolayer demonstrated that K8 as well as K14 were incorporated in the cellular cytoskeleton [15].

Associations of Krt14 with chemical compounds

  • The subcolumnar reserve cells induced by vitamin A deficiency displayed positive staining for K5 and K14 [16].
  • However, low level of phenylalanine clearance was observed in mice expressing PAH and GTP-CH from the K14 promoter, suggesting that the skin can be genetically engineered to function as a 'metabolic sink' [17].
  • Keratin 14 was consistently expressed by mammary basal cells, and was detected in scattered luminal cells from 13.5 days after conception through puberty [18].
  • In cell culture, the INV and K14 promoter constructs demonstrated significant beta-galactosidase expression in human keratinocytes, but minimal expression in 293 and NIH 3T3 cell types [19].
  • However, the epithelial cell lines expressed cytokeratin 14 and cytokeratin 10 when exposed to medium containing different concentrations of Ca(2+) [20].

Regulatory relationships of Krt14


Other interactions of Krt14

  • The K1/K14 pair was capable of forming a cytoskeletal network, but the network was poorly developed, and usually perinuclear [12].
  • A distinct mTEC subset binds UEA-1 and expresses K8, but not K5 or K14 [26].
  • The distribution of K5, the natural partner of K14, at the immunofluorescence level was also normal looking in the K14-/- MKC-5 cells, but with fewer filaments detectable, consistent with the approximately 20% reduction in K5 detectable on immunoblots [14].
  • K17 expression was increased approximately 40% in the K14-/- cells [14].
  • Nipple connective tissue and its development: insights from the K14-PTHrP mouse [27].

Analytical, diagnostic and therapeutic context of Krt14


  1. The basal keratin network of stratified squamous epithelia: defining K15 function in the absence of K14. Lloyd, C., Yu, Q.C., Cheng, J., Turksen, K., Degenstein, L., Hutton, E., Fuchs, E. J. Cell Biol. (1995) [Pubmed]
  2. Transcriptional control of high molecular weight keratin gene expression in multistage mouse skin carcinogenesis. Roop, D.R., Krieg, T.M., Mehrel, T., Cheng, C.K., Yuspa, S.H. Cancer Res. (1988) [Pubmed]
  3. Parathyroid hormone-related protein is required for tooth eruption. Philbrick, W.M., Dreyer, B.E., Nakchbandi, I.A., Karaplis, A.C. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  4. Induction of ornithine decarboxylase activity is a necessary step for mitogen-activated protein kinase kinase-induced skin tumorigenesis. Feith, D.J., Bol, D.K., Carboni, J.M., Lynch, M.J., Sass-Kuhn, S., Shoop, P.L., Shantz, L.M. Cancer Res. (2005) [Pubmed]
  5. Deacetylation of the herpes simplex virus type 1 latency-associated transcript (LAT) enhancer and a decrease in LAT abundance precede an increase in ICP0 transcriptional permissiveness at early times postexplant. Amelio, A.L., Giordani, N.V., Kubat, N.J., O'neil, J.E., Bloom, D.C. J. Virol. (2006) [Pubmed]
  6. Deregulated expression of c-Myc depletes epidermal stem cells. Waikel, R.L., Kawachi, Y., Waikel, P.A., Wang, X.J., Roop, D.R. Nat. Genet. (2001) [Pubmed]
  7. Point mutations in human keratin 14 genes of epidermolysis bullosa simplex patients: genetic and functional analyses. Coulombe, P.A., Hutton, M.E., Letai, A., Hebert, A., Paller, A.S., Fuchs, E. Cell (1991) [Pubmed]
  8. IL-7 overexpression in transgenic mouse keratinocytes causes a lymphoproliferative skin disease dominated by intermediate TCR cells: evidence for a hierarchy in IL-7 responsiveness among cutaneous T cells. Williams, I.R., Rawson, E.A., Manning, L., Karaoli, T., Rich, B.E., Kupper, T.S. J. Immunol. (1997) [Pubmed]
  9. Oral cavity and esophageal carcinogenesis modeled in carcinogen-treated mice. Tang, X.H., Knudsen, B., Bemis, D., Tickoo, S., Gudas, L.J. Clin. Cancer Res. (2004) [Pubmed]
  10. Targeted somatic mutagenesis in mouse epidermis. Indra, A.K., Li, M., Brocard, J., Warot, X., Bornert, J.M., Gérard, C., Messaddeq, N., Chambon, P., Metzger, D. Horm. Res. (2000) [Pubmed]
  11. The functional diversity of epidermal keratins revealed by the partial rescue of the keratin 14 null phenotype by keratin 16. Paladini, R.D., Coulombe, P.A. J. Cell Biol. (1999) [Pubmed]
  12. Mouse differentiation-specific keratins 1 and 10 require a preexisting keratin scaffold to form a filament network. Kartasova, T., Roop, D.R., Holbrook, K.A., Yuspa, S.H. J. Cell Biol. (1993) [Pubmed]
  13. Progressive squamous epithelial neoplasia in K14-human papillomavirus type 16 transgenic mice. Arbeit, J.M., Münger, K., Howley, P.M., Hanahan, D. J. Virol. (1994) [Pubmed]
  14. In vitro characteristics of early epidermal progenitors isolated from keratin 14 (K14)-deficient mice: insights into the role of keratin 17 in mouse keratinocytes. Troy, T.C., Turksen, K. J. Cell. Physiol. (1999) [Pubmed]
  15. Keratin 14 protein in cultured nonparenchymal rat hepatic epithelial cells: characterization of keratin 14 and keratin 19 as antigens for the commonly used mouse monoclonal antibody OV-6. Bisgaard, H.C., Parmelee, D.C., Dunsford, H.A., Sechi, S., Thorgeirsson, S.S. Mol. Carcinog. (1993) [Pubmed]
  16. Retinoid status controls the appearance of reserve cells and keratin expression in mouse cervical epithelium. Darwiche, N., Celli, G., Sly, L., Lancillotti, F., De Luca, L.M. Cancer Res. (1993) [Pubmed]
  17. Characterization of transgenic mice with the expression of phenylalanine hydroxylase and GTP cyclohydrolase I in the skin. Christensen, R., Alhonen, L., Wahlfors, J., Jakobsen, M., Jensen, T.G. Exp. Dermatol. (2005) [Pubmed]
  18. Expression of terminal differentiation proteins defines stages of mouse mammary gland development. Mikaelian, I., Hovick, M., Silva, K.A., Burzenski, L.M., Shultz, L.D., Ackert-Bicknell, C.L., Cox, G.A., Sundberg, J.P. Vet. Pathol. (2006) [Pubmed]
  19. Differential expression of tissue-specific promoters by gene gun. Lin, M.T., Wang, F., Uitto, J., Yoon, K. Br. J. Dermatol. (2001) [Pubmed]
  20. Establishment and characterization of clonal cell lines from the vagina of p53-deficient young mice. Tanahashi, K., Shibahara, S., Ogawa, M., Hanazono, M., Aizawa, S., Tomooka, Y. In Vitro Cell. Dev. Biol. Anim. (2002) [Pubmed]
  21. Phenotypic modulation of keratins, vimentin, and alpha-fetoprotein in cultured rat liver epithelial cells after chemical, oncogene, and spontaneous transformation. Bisgaard, H.C., Ton, P.T., Nagy, P., Thorgeirsson, S.S. J. Cell. Physiol. (1994) [Pubmed]
  22. Expression of keratin 12 and maturation of corneal epithelium during development and postnatal growth. Tanifuji-Terai, N., Terai, K., Hayashi, Y., Chikama, T., Kao, W.W. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  23. Hair follicle apoptosis and Bcl-2. Müller-Röver, S., Rossiter, H., Lindner, G., Peters, E.M., Kupper, T.S., Paus, R. J. Investig. Dermatol. Symp. Proc. (1999) [Pubmed]
  24. Overexpression of activin A in the skin of transgenic mice reveals new activities of activin in epidermal morphogenesis, dermal fibrosis and wound repair. Munz, B., Smola, H., Engelhardt, F., Bleuel, K., Brauchle, M., Lein, I., Evans, L.W., Huylebroeck, D., Balling, R., Werner, S. EMBO J. (1999) [Pubmed]
  25. Overexpression of the calcium sensing receptor accelerates epidermal differentiation and permeability barrier formation in vivo. Turksen, K., Troy, T.C. Mech. Dev. (2003) [Pubmed]
  26. Thymus Medulla Formation and Central Tolerance Are Restored in IKK{alpha}-/- Mice That Express an IKK{alpha} Transgene in Keratin 5+ Thymic Epithelial Cells. Lomada, D., Liu, B., Coghlan, L., Hu, Y., Richie, E.R. J. Immunol. (2007) [Pubmed]
  27. Nipple connective tissue and its development: insights from the K14-PTHrP mouse. Abdalkhani, A., Sellers, R., Gent, J., Wulitich, H., Childress, S., Stein, B., Boissy, R.E., Wysolmerski, J.J., Foley, J. Mech. Dev. (2002) [Pubmed]
  28. Sonic hedgehog regulates prostatic growth and epithelial differentiation. Freestone, S.H., Marker, P., Grace, O.C., Tomlinson, D.C., Cunha, G.R., Harnden, P., Thomson, A.A. Dev. Biol. (2003) [Pubmed]
  29. Conversion of columnar to stratified squamous epithelium in the developing mouse oesophagus. Yu, W.Y., Slack, J.M., Tosh, D. Dev. Biol. (2005) [Pubmed]
  30. An inducible mouse model for epidermolysis bullosa simplex: implications for gene therapy. Cao, T., Longley, M.A., Wang, X.J., Roop, D.R. J. Cell Biol. (2001) [Pubmed]
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