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Gene Review

Krt8  -  keratin 8

Mus musculus

Synonyms: AA960620, AL022697, AU019895, CK-8, Card2, ...
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Disease relevance of Krt8


High impact information on Krt8

  • Our results demonstrate that genetic modifiers of K8/K18 filament functions, with profound effects on embryogenesis and gut functional integrity, are differentially active in the FVB/N and C57B1/6 genetic backgrounds [6].
  • Colorectal hyperplasia and inflammation in keratin 8-deficient FVB/N mice [6].
  • The intermediate filament protein keratin 8 (K8) is critical for the development of most mouse embryos beyond midgestation [2].
  • We conclude the lethality of K8-/- embryos is due to a TNF-sensitive failure of trophoblast giant cell barrier function [2].
  • In vivo, after injection into the cleared mammary fat pad, these cells gave rise to bilayered, hollow, alveolus-like structures comprising basal cells expressing cytokeratin 5 and luminal cells positive for cytokeratin 8 and secreting beta-casein in a polarized manner into the lumen [7].

Chemical compound and disease context of Krt8


Biological context of Krt8

  • Functional studies with different cell models have suggested that K8/K18 are involved in simple epithelial cell resistance to several forms of stress that may lead to cell death [9].
  • Here, we report an additional abnormal liver phenotype, which is similar in K8 null, K18 null, and K18C mouse models [10].
  • These effects could stem from disturbed functions of K8/18-dependent cell-cycle regulators, such as the signaling integrator, 14-3-3 [10].
  • Analysis of normal gut-specific homing molecules, reveals an increased number of alpha(4)beta(7)-positive cells and vascular mucosal addressin cell adhesion molecule-1 in K8-null colons [3].
  • EndoA cytokeratin (EndoA) belongs to a family of intermediate filaments (IFs) and is coordinately expressed with EndoB cytokeratin during early mouse embryogenesis [11].

Anatomical context of Krt8

  • These hepatocyte cytoplasmic deposits are composed primarily of hyperphosphorylated keratins 8 and 18 (K8/K18) [12].
  • Colon lymphocytes were isolated for analysis of their phenotype and cytokine production, and vascular and lymphocyte adhesion molecule expression in K8-/- mice of varying ages [3].
  • In tumors induced by the cell lines upon injection in mice, K8 is found in the less differentiated regions as opposite to K13, restricted to the differentiating areas of the tumors [4].
  • Immunocytochemical analysis of the cells in monolayer demonstrated that K8 as well as K14 were incorporated in the cellular cytoskeleton [13].
  • It demonstrates that the latency, but not the incidence nor the morphological features, of PyV middle T-induced mammary gland tumours is affected by keratin 8 deficiency [5].

Associations of Krt8 with chemical compounds

  • Labeling for K8/18 of luminal cells was heterogeneous at all times [14].
  • Similarly, cytokeratin-8 (CK-8) levels were markedly increased in the liver homogenates of rats fed ethanol when given PS-341 [15].
  • Antibodies to specific serine phosphorylated sites 73 and 431, located in cytokeratin 8, localized to Mallory bodies in vivo, indicating that cytokeratin 8 was hyperphosphorylated [16].
  • Furthermore, differentiation in presence of Bt2cAMP plus RA resulted in an earlier induction of the two mRNAs and a higher level of expression of K8 mRNA [17].
  • Like DDC refeeding, both CBDL and CA feeding of drug-primed mice significantly increased CK 8 and CK 18 mRNA and protein levels (with excess of CK 8) and resulted in ubiquitination and abnormal phosphorylation of CKs [18].

Physical interactions of Krt8


Co-localisations of Krt8

  • On the other hand, K8 does not generally colocalize with K13, a keratin also aberrantly expressed by epidermal cell cultures when induced to differentiate by high Ca2+ medium [4].

Regulatory relationships of Krt8


Other interactions of Krt8

  • The lethality resulted from defects in the placenta where both K19 and K8 are normally expressed [24].
  • In contrast, K6, K8, K13 and K14 are constitutively expressed even when squamous differentiation is not observed [25].
  • In colonies of both phenotypes, only a few cells expressed K5 and bcl-2, while all cells expressed K8 [26].
  • Our ICC assay showed that differentiating cells did not express hepatic proteins, such as AFP, ALB, CK8, and CK18 until day 7, day 9, day 11, and day 11, respectively (up to 2 days later when growth factors are not present) [27].
  • The cells were double stained using CK-8 and ubiquitin antibodies [28].

Analytical, diagnostic and therapeutic context of Krt8


  1. Keratins modulate colonocyte electrolyte transport via protein mistargeting. Toivola, D.M., Krishnan, S., Binder, H.J., Singh, S.K., Omary, M.B. J. Cell Biol. (2004) [Pubmed]
  2. Keratin 8 protection of placental barrier function. Jaquemar, D., Kupriyanov, S., Wankell, M., Avis, J., Benirschke, K., Baribault, H., Oshima, R.G. J. Cell Biol. (2003) [Pubmed]
  3. Keratin-8-deficient mice develop chronic spontaneous Th2 colitis amenable to antibiotic treatment. Habtezion, A., Toivola, D.M., Butcher, E.C., Omary, M.B. J. Cell. Sci. (2005) [Pubmed]
  4. Changes in keratin expression during malignant progression of transformed mouse epidermal keratinocytes. Caulín, C., Bauluz, C., Gandarillas, A., Cano, A., Quintanilla, M. Exp. Cell Res. (1993) [Pubmed]
  5. Functional analysis of mouse keratin 8 in polyoma middle T-induced mammary gland tumours. Baribault, H., Wilson-Heiner, M., Muller, W., Penner, J., Bakhiet, N. Transgenic Res. (1997) [Pubmed]
  6. Colorectal hyperplasia and inflammation in keratin 8-deficient FVB/N mice. Baribault, H., Penner, J., Iozzo, R.V., Wilson-Heiner, M. Genes Dev. (1994) [Pubmed]
  7. EGF controls the in vivo developmental potential of a mammary epithelial cell line possessing progenitor properties. Deugnier, M.A., Faraldo, M.M., Janji, B., Rousselle, P., Thiery, J.P., Glukhova, M.A. J. Cell Biol. (2002) [Pubmed]
  8. Sequence of EndoA gene encoding mouse cytokeratin and its methylation state in the CpG-rich region. Tamai, Y., Takemoto, Y., Matsumoto, M., Morita, T., Matsushiro, A., Nozaki, M. Gene (1991) [Pubmed]
  9. Keratins modulate c-Flip/extracellular signal-regulated kinase 1 and 2 antiapoptotic signaling in simple epithelial cells. Gilbert, S., Loranger, A., Marceau, N. Mol. Cell. Biol. (2004) [Pubmed]
  10. Disturbances in hepatic cell-cycle regulation in mice with assembly-deficient keratins 8/18. Toivola, D.M., Nieminen, M.I., Hesse, M., He, T., Baribault, H., Magin, T.M., Omary, M.B., Eriksson, J.E. Hepatology (2001) [Pubmed]
  11. Nucleotide sequence of mouse EndoA cytokeratin cDNA reveals polypeptide characteristics of the type-II keratin subfamily. Morita, T., Tondella, M.L., Takemoto, Y., Hashido, K., Ichinose, Y., Nozaki, M., Matsushiro, A. Gene (1988) [Pubmed]
  12. Keratin 18 overexpression but not phosphorylation or filament organization blocks mouse Mallory body formation. Harada, M., Strnad, P., Resurreccion, E.Z., Ku, N.O., Omary, M.B. Hepatology (2007) [Pubmed]
  13. 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]
  14. 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]
  15. Proteasome inhibition induces cytokeratin accumulation in vivo. Bardag-Gorce, F., Vu, J., Nan, L., Riley, N., Li, J., French, S.W. Exp. Mol. Pathol. (2004) [Pubmed]
  16. Mallory body (cytokeratin aggresomes) formation is prevented in vitro by p38 inhibitor. Nan, L., Dedes, J., French, B.A., Bardag-Gorce, F., Li, J., Wu, Y., French, S.W. Exp. Mol. Pathol. (2006) [Pubmed]
  17. Differential regulation of keratin 8 and 18 messenger RNAs in differentiating F9 cells. Ouellet, T., Lampron, C., Lussier, M., Lapointe, L., Royal, A. Biochim. Biophys. Acta (1990) [Pubmed]
  18. Bile acid-induced Mallory body formation in drug-primed mouse liver. Fickert, P., Trauner, M., Fuchsbichler, A., Stumptner, C., Zatloukal, K., Denk, H. Am. J. Pathol. (2002) [Pubmed]
  19. Sequence specific binding of Ets-1 to the mouse cytokeratin EndoA gene enhancer. Hamazato, F., Fujimura, Y., Tamai, Y., Takemoto, Y., Matsushiro, A., Nozaki, M. Biochem. Biophys. Res. Commun. (1993) [Pubmed]
  20. One of two Ets-binding sites in the cytokeratin EndoA enhancer is essential for enhancer activity and binds to Ets-2 related proteins. Fujimura, Y., Yamamoto, H., Hamazato, F., Nozaki, M. Nucleic Acids Res. (1994) [Pubmed]
  21. Intranasal vaccination with a secreted chlamydial protein enhances resolution of genital Chlamydia muridarum infection, protects against oviduct pathology, and is highly dependent upon endogenous gamma interferon production. Murthy, A.K., Chambers, J.P., Meier, P.A., Zhong, G., Arulanandam, B.P. Infect. Immun. (2007) [Pubmed]
  22. The suprabasal expression of alpha 6 beta 4 integrin is associated with a high risk for malignant progression in mouse skin carcinogenesis. Tennenbaum, T., Weiner, A.K., Belanger, A.J., Glick, A.B., Hennings, H., Yuspa, S.H. Cancer Res. (1993) [Pubmed]
  23. Simple epithelium keratins 8 and 18 provide resistance to Fas-mediated apoptosis. The protection occurs through a receptor-targeting modulation. Gilbert, S., Loranger, A., Daigle, N., Marceau, N. J. Cell Biol. (2001) [Pubmed]
  24. Cytokeratins 8 and 19 in the mouse placental development. Tamai, Y., Ishikawa, T., Bösl, M.R., Mori, M., Nozaki, M., Baribault, H., Oshima, R.G., Taketo, M.M. J. Cell Biol. (2000) [Pubmed]
  25. Expression of keratins in mouse vaginal epithelium. Gimenez-Conti, I.B., Lynch, M., Roop, D., Bhowmik, S., Majeski, P., Conti, C.J. Differentiation (1994) [Pubmed]
  26. Evidence for stem cells in cultures of mouse prostate epithelial cells. Sawicki, J.A., Rothman, C.J. Prostate (2002) [Pubmed]
  27. Hepatic differentiation from embryonic stem cells in vitro. Hu, A., Cai, J., Zheng, Q., He, X., Pan, Y., Li, L. Chin. Med. J. (2003) [Pubmed]
  28. The mechanism of cytokeratin aggresome formation: the role of mutant ubiquitin (UBB+1). Bardag-Gorce, F., Riley, N., Nguyen, V., Montgomery, R.O., French, B.A., Li, J., van Leeuwen, F.W., Lungo, W., McPhaul, L.W., French, S.W. Exp. Mol. Pathol. (2003) [Pubmed]
  29. Patterns of keratins 8, 18 and 19 during gonadal differentiation in the mouse: sex- and time-dependent expression of keratin 19. Appert, A., Fridmacher, V., Locquet, O., Magre, S. Differentiation (1998) [Pubmed]
  30. Conversion of columnar to stratified squamous epithelium in the developing mouse oesophagus. Yu, W.Y., Slack, J.M., Tosh, D. Dev. Biol. (2005) [Pubmed]
  31. Aberrant expression of the simple epithelial type II keratin 8 by mouse skin carcinomas but not papillomas. Larcher, F., Bauluz, C., Díaz-Guerra, M., Quintanilla, M., Conti, C.J., Ballestín, C., Jorcano, J.L. Mol. Carcinog. (1992) [Pubmed]
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