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Gene Review

Krt12  -  keratin 12

Mus musculus

Synonyms: AI835216, CK-12, Cytokeratin-12, K12, Keratin, type I cytoskeletal 12, ...
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Disease relevance of A830036E02Rik

  • Lateral transfer of genes is frequent, with 11% of the S. typhimurium LT2 genes missing from S. enterica serovar Typhi (S. typhi), and 29% missing from Escherichia coli K12 [1].
  • Expression of the keratin-12 and aquaporin-5 genes was downregulated, consistent with the Klf4CN corneal epithelial fragility and stromal edema, respectively [2].
  • This disaccharide seems free and accessible on the basis of the previously calculated conformations of the Salmonella (Ra) and E. coli complete cores (R1, R2, R3, R4, and K12) [3].
  • We have previously reported that, unlike Escherichia coli K12, intracellular pathogens from the genus Brucella survive and multiply within U937-derived phagocytes, and live Brucella organisms failed to induce TNF-alpha release upon infection [4].
  • The results show that the K12/TR system can be used as a model to study metastasis of colon carcinoma cells and may find utility in the testing of chemotherapeutic agents against metastatic lesions [5].

High impact information on A830036E02Rik

  • Pathogenicity of conventional and debilitated Escherichia coli K12 [6].
  • Herpes simplex virus thymidine kinase activity of thymidine kinase-deficient Escherichia coli K-12 mutant transformed by hybrid plasmids [7].
  • We find that cells with conditional (temperature-sensitive) defects in protein glycosylation (CHO K12 and BHK tsBN7) induce CHOP when cultured at the nonpermissive temperature [8].
  • The distinctive differences in metabolic profiles of K12 and K13 codon mutated cells indicate that a strong correlation exists between the flow of glucose carbons towards either increased anaerobic glycolysis, and resistance to apoptosis (K12), or increased macromolecule synthesis, rapid proliferation, and increased sensitivity to apoptosis [9].
  • We evaluated changes in morphology, proliferative capacity, contact inhibition, and predisposition to apoptosis and anchorage-independent growth in K12, K13, and Kwt-oe transformants [10].

Chemical compound and disease context of A830036E02Rik


Biological context of A830036E02Rik


Anatomical context of A830036E02Rik

  • At later developmental stages only suprabasal corneal epithelium expressed K12, however, in post-natal and adult cornea all cell layers were K12-positive [19].
  • K12 was first detected in corneal epithelial cells of day 15 mouse embryos in a small subpopulation of superficial cells [19].
  • Expression of keratins K12, K4 and K14 during development of ocular surface epithelium [19].
  • RESULTS: Northern hybridization, RT-PCR and Western blot analysis revealed that mHa 1, 2, 3 and 4 keratins are expressed in the skin, but not in cornea, whereas the expression of K12 is limited to the corneas of the Bsk mice [16].
  • METHODS: One allele of murine Krt1.12 gene was ablated in the embryonic stem cell line, E14.1, by homologous recombination with a DNA construct in which the DNA element between intron 2 and exon 8 of the keratin 12 gene was replaced by a neo-gene [20].

Associations of A830036E02Rik with chemical compounds

  • Despite the presence of the capsular polysaccharide, the O1 antigen was exposed at the cell surface in strains producing K2, K7, K8, K12, K19, K21, K22, K34, K35, K42, K45, K55, K57, K62, K66, K69, and K70 capsular polysaccharides [21].
  • Immunoblot analysis revealed that K12 expression was the highest in SHEM/SHEM, decreased from passages 0 to 1, and disappeared in passage 2 in KSFM/KSFM, with complete replacement of K10 and increasing expression of involucrin [22].
  • Serum from rats treated with i.v. cinchonine produced greater uptake of doxorubicin in cancer cells (DHD/K12/PROb rat colon cells and K562/ADM human leukemic cells) than did serum from quinine-treated rats (ex vivo assay) [23].
  • Cinchonine was more effective than quinine in reducing tumor mass and increasing the survival of rats inoculated i.p. with DHD/K12/PROb cells and treated i.p. with deoxydoxorubicin [23].
  • The K12/TR cell line was derived from a transplantable colon carcinoma induced by dimethylhydrazine in the BD-1X rat strain [5].

Regulatory relationships of A830036E02Rik

  • The number of K14-positive cells that coexpressed K12 increased with age and reached a plateau after P180 [17].

Other interactions of A830036E02Rik

  • 5. In the period from E15.5 to P10, the expression of K12 was restricted to the suprabasal and/or superficial cells of the corneal epithelium, whereas the K14 expression was restricted to the basal cells [17].
  • ESE-1 transactivates through the regulatory element of cornea-specific K12 keratin [24].
  • Keratin 12 expression was not altered in Tgfb2(-/-) mice, implicating normal corneal type epithelial differentiation [25].
  • Computer analysis of the data for total radioactivity (PCNU equivalents), based upon an open two-compartment model, yielded values of the pharmacokinetic parameters K12, K21, and K10 of 1.49 hr-1, 0.25 hr-1, and 0.19 hr-1, respectively [26].
  • Conjunctival epithelial cells can resurface denuded cornea, but do not transdifferentiate to express cornea-specific keratin 12 following removal of limbal epithelium in mouse [27].

Analytical, diagnostic and therapeutic context of A830036E02Rik


  1. Complete genome sequence of Salmonella enterica serovar Typhimurium LT2. McClelland, M., Sanderson, K.E., Spieth, J., Clifton, S.W., Latreille, P., Courtney, L., Porwollik, S., Ali, J., Dante, M., Du, F., Hou, S., Layman, D., Leonard, S., Nguyen, C., Scott, K., Holmes, A., Grewal, N., Mulvaney, E., Ryan, E., Sun, H., Florea, L., Miller, W., Stoneking, T., Nhan, M., Waterston, R., Wilson, R.K. Nature (2001) [Pubmed]
  2. Conditional deletion of the mouse Klf4 gene results in corneal epithelial fragility, stromal edema, and loss of conjunctival goblet cells. Swamynathan, S.K., Katz, J.P., Kaestner, K.H., Ashery-Padan, R., Crawford, M.A., Piatigorsky, J. Mol. Cell. Biol. (2007) [Pubmed]
  3. The disaccharide L-alpha-D-heptose1-->7-L-alpha-D-heptose1-->of the inner core domain of Salmonella lipopolysaccharide is accessible to antibody and is the epitope of a broadly reactive monoclonal antibody. Nnalue, N.A., Lind, S.M., Lindberg, A.A. J. Immunol. (1992) [Pubmed]
  4. Brucella species release a specific, protease-sensitive, inhibitor of TNF-alpha expression, active on human macrophage-like cells. Caron, E., Gross, A., Liautard, J.P., Dornand, J. J. Immunol. (1996) [Pubmed]
  5. Characterization of an animal model of metastatic colon carcinoma. Dunnington, D.J., Buscarino, C., Gennaro, D., Greig, R., Poste, G. Int. J. Cancer (1987) [Pubmed]
  6. Pathogenicity of conventional and debilitated Escherichia coli K12. Levy, S.B., Sullivan, N., Gorbach, S.L. Nature (1978) [Pubmed]
  7. Herpes simplex virus thymidine kinase activity of thymidine kinase-deficient Escherichia coli K-12 mutant transformed by hybrid plasmids. Kit, S., Otsuka, H., Qavi, H., Hazen, M. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  8. Signals from the stressed endoplasmic reticulum induce C/EBP-homologous protein (CHOP/GADD153). Wang, X.Z., Lawson, B., Brewer, J.W., Zinszner, H., Sanjay, A., Mi, L.J., Boorstein, R., Kreibich, G., Hendershot, L.M., Ron, D. Mol. Cell. Biol. (1996) [Pubmed]
  9. K-ras codon-specific mutations produce distinctive metabolic phenotypes in NIH3T3 mice [corrected] fibroblasts. Vizan, P., Boros, L.G., Figueras, A., Capella, G., Mangues, R., Bassilian, S., Lim, S., Lee, W.N., Cascante, M. Cancer Res. (2005) [Pubmed]
  10. K-ras codon 12 mutation induces higher level of resistance to apoptosis and predisposition to anchorage-independent growth than codon 13 mutation or proto-oncogene overexpression. Guerrero, S., Casanova, I., Farré, L., Mazo, A., Capellà, G., Mangues, R. Cancer Res. (2000) [Pubmed]
  11. The transfer of a bacterial transmembrane function to eukaryotic cells. Lo, T.C. J. Biol. Chem. (1979) [Pubmed]
  12. Relationships among capsular structure, phagocytosis, and mouse virulence in Klebsiella pneumoniae. Kabha, K., Nissimov, L., Athamna, A., Keisari, Y., Parolis, H., Parolis, L.A., Grue, R.M., Schlepper-Schafer, J., Ezekowitz, A.R., Ohman, D.E. Infect. Immun. (1995) [Pubmed]
  13. The Escherichia coli K-12 gntP gene allows E. coli F-18 to occupy a distinct nutritional niche in the streptomycin-treated mouse large intestine. Sweeney, N.J., Klemm, P., McCormick, B.A., Moller-Nielsen, E., Utley, M., Schembri, M.A., Laux, D.C., Cohen, P.S. Infect. Immun. (1996) [Pubmed]
  14. Peptide mass mapping of acetylated isoforms of histone H4 from mouse lymphosarcoma cells treated with histone deacetylase (HDACs) inhibitors. Ren, C., Zhang, L., Freitas, M.A., Ghoshal, K., Parthun, M.R., Jacob, S.T. J. Am. Soc. Mass Spectrom. (2005) [Pubmed]
  15. Expression and immunogenicity of the V3 loop from the envelope of human immunodeficiency virus type 1 in an attenuated aroA strain of Salmonella typhimurium upon genetic coupling to two Escherichia coli carrier proteins. Charbit, A., Martineau, P., Ronco, J., Leclerc, C., Lo-Man, R., Michel, V., O'Callaghan, D., Hofnung, M. Vaccine (1993) [Pubmed]
  16. Characterization of Bsk mice: I. The Bsk mutation does not involve a recombination of cornea-specific keratin 12 and skin-specific hair keratin genes. Shiraishi, A., Kao, C.W., Ishizaki, M., Zhang, Z., Converse, R.L., Tseng, S.C., Svoboda, K.K., Kao, W.W. Curr. Eye Res. (1998) [Pubmed]
  17. 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]
  18. Characterization and chromosomal localization of the cornea-specific murine keratin gene Krt1.12. Liu, C.Y., Zhu, G., Converse, R., Kao, C.W., Nakamura, H., Tseng, S.C., Mui, M.M., Seyer, J., Justice, M.J., Stech, M.E. J. Biol. Chem. (1994) [Pubmed]
  19. Expression of keratins K12, K4 and K14 during development of ocular surface epithelium. Kurpakus, M.A., Maniaci, M.T., Esco, M. Curr. Eye Res. (1994) [Pubmed]
  20. Keratin 12-deficient mice have fragile corneal epithelia. Kao, W.W., Liu, C.Y., Converse, R.L., Shiraishi, A., Kao, C.W., Ishizaki, M., Doetschman, T., Duffy, J. Invest. Ophthalmol. Vis. Sci. (1996) [Pubmed]
  21. Surface exposure of O1 serotype lipopolysaccharide in Klebsiella pneumoniae strains expressing different K antigens. Tomás, J.M., Camprubi, S., Merino, S., Davey, M.R., Williams, P. Infect. Immun. (1991) [Pubmed]
  22. Calcium-induced abnormal epidermal-like differentiation in cultures of mouse corneal-limbal epithelial cells. Kawakita, T., Espana, E.M., He, H., Yeh, L.K., Liu, C.Y., Tseng, S.C. Invest. Ophthalmol. Vis. Sci. (2004) [Pubmed]
  23. Cinchonine, a potent efflux inhibitor to circumvent anthracycline resistance in vivo. Genne, P., Dimanche-Boitrel, M.T., Mauvernay, R.Y., Gutierrez, G., Duchamp, O., Petit, J.M., Martin, F., Chauffert, B. Cancer Res. (1992) [Pubmed]
  24. Ets family transcription factor ESE-1 is expressed in corneal epithelial cells and is involved in their differentiation. Yoshida, N., Yoshida, S., Araie, M., Handa, H., Nabeshima, Y. Mech. Dev. (2000) [Pubmed]
  25. TGFbeta2 in corneal morphogenesis during mouse embryonic development. Saika, S., Saika, S., Liu, C.Y., Azhar, M., Sanford, L.P., Doetschman, T., Gendron, R.L., Kao, C.W., Kao, W.W. Dev. Biol. (2001) [Pubmed]
  26. Pharmacological disposition of 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosourea in mice. Rahman, A., Luc, P.V., Schein, P.S., Woolley, P.V. Cancer Res. (1984) [Pubmed]
  27. Conjunctival epithelial cells can resurface denuded cornea, but do not transdifferentiate to express cornea-specific keratin 12 following removal of limbal epithelium in mouse. Moyer, P.D., Kaufman, A.H., Zhang, Z., Kao, C.W., Spaulding, A.G., Kao, W.W. Differentiation (1996) [Pubmed]
  28. Cornea-specific expression of K12 keratin during mouse development. Liu, C.Y., Zhu, G., Westerhausen-Larson, A., Converse, R., Kao, C.W., Sun, T.T., Kao, W.W. Curr. Eye Res. (1993) [Pubmed]
  29. Requirement for Pax6 in corneal morphogenesis: a role in adhesion. Davis, J., Duncan, M.K., Robison, W.G., Piatigorsky, J. J. Cell. Sci. (2003) [Pubmed]
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