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Gene Review

Gjb2  -  gap junction protein, beta 2

Mus musculus

Synonyms: AI325222, Cnx26, Connexin-26, Cx26, Cxn-26, ...
 
 
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Disease relevance of Gjb2

  • No hyperproliferation or hyperplasia was observed, suggesting that Cx26 does not function as a tumor suppressor [1].
  • In papillomas, no clear reduction of the two connexins was observed; however, Cx26 and Cx43 were frequently co-localized in the same gap junction plaques, whereas the two kinds of Cxs were differentially expressed in normal and surrounding non-tumorous epidermis [2].
  • Squamous cell carcinomas at invasive sites showed clear reduction of Cx26 and Cx43 [2].
  • The channel properties responsible for producing the rectifying current observed for Cx26/Cx32 heterotypic gap junction channels were determined in transfected mouse neuroblastoma 2A (N2A) cells [3].
  • This suggests that, during the acute-phase response, the second hepatic Cx26 protein may compensate in part for the downregulation of the Cx32 protein [4].
 

High impact information on Gjb2

  • We provide support for this approach and report the identification of mutations in the gene (Gjb2) encoding connexin 26, using archives established from the UK ENU mutagenesis program [5].
  • Here we study a pedigree containing cases of autosomal dominant deafness and have identified a mutation in the gene encoding the gap-junction protein connexin 26 (Cx26) that segregates with the profound deafness in the family [6].
  • The same antibodies bound connexin 26, gene mutations of which lead to congenital inner-ear deafness [7].
  • We generated mice in which extra copies of the Cx26 gene were transgenically expressed from a modified bacterial artificial chromosome in a Cx30(-/-) background [8].
  • In the absence of the Cx30 gene, Cx26 expressed from extra alleles completely restored hearing sensitivity and prevented hair cell death in deaf Cx30(-/-) mice [8].
 

Chemical compound and disease context of Gjb2

 

Biological context of Gjb2

 

Anatomical context of Gjb2

 

Associations of Gjb2 with chemical compounds

 

Regulatory relationships of Gjb2

  • Previously, we found increased formation of chemically induced liver tumours but no increase in spontaneous development of preneoplastic hepatic foci in mice that lacked Cx32 and expressed decreased amounts of Cx26 [17].
  • Cx26 immunofluorescence and a beta-gal reporter under regulatory control of the Cx36 promoter did not colocalize with a horizontal cell marker, indicating that these genes are not expressed by horizontal cells [22].
  • In addition, FA strongly induced metallothionein 1 expression and inhibited connexin 26 expression in skin but did not affect expression of these genes in tumors [23].
 

Other interactions of Gjb2

 

Analytical, diagnostic and therapeutic context of Gjb2

References

  1. Loss of connexin 26 in mammary epithelium during early but not during late pregnancy results in unscheduled apoptosis and impaired development. Bry, C., Maass, K., Miyoshi, K., Willecke, K., Ott, T., Robinson, G.W., Hennighausen, L. Dev. Biol. (2004) [Pubmed]
  2. Aberrant expression of gap junction proteins (connexins) is associated with tumor progression during multistage mouse skin carcinogenesis in vivo. Kamibayashi, Y., Oyamada, Y., Mori, M., Oyamada, M. Carcinogenesis (1995) [Pubmed]
  3. Different ionic selectivities for connexins 26 and 32 produce rectifying gap junction channels. Suchyna, T.M., Nitsche, J.M., Chilton, M., Harris, A.L., Veenstra, R.D., Nicholson, B.J. Biophys. J. (1999) [Pubmed]
  4. Downregulation of connexin32 protein and gap-junctional intercellular communication by cytokine-mediated acute-phase response in immortalized mouse hepatocytes. Temme, A., Traub, O., Willecke, K. Cell Tissue Res. (1998) [Pubmed]
  5. A gene-driven approach to the identification of ENU mutants in the mouse. Coghill, E.L., Hugill, A., Parkinson, N., Davison, C., Glenister, P., Clements, S., Hunter, J., Cox, R.D., Brown, S.D. Nat. Genet. (2002) [Pubmed]
  6. Connexin 26 mutations in hereditary non-syndromic sensorineural deafness. Kelsell, D.P., Dunlop, J., Stevens, H.P., Lench, N.J., Liang, J.N., Parry, G., Mueller, R.F., Leigh, I.M. Nature (1997) [Pubmed]
  7. Autoantibodies to inner ear and endothelial antigens in Cogan's syndrome. Lunardi, C., Bason, C., Leandri, M., Navone, R., Lestani, M., Millo, E., Benatti, U., Cilli, M., Beri, R., Corrocher, R., Puccetti, A. Lancet (2002) [Pubmed]
  8. Restoration of connexin26 protein level in the cochlea completely rescues hearing in a mouse model of human connexin30-linked deafness. Ahmad, S., Tang, W., Chang, Q., Qu, Y., Hibshman, J., Li, Y., Söhl, G., Willecke, K., Chen, P., Lin, X. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  9. Quantitative analysis of gap-junctional intercellular communication in precision-cut mouse liver slices. Romualdi, A., Niessen, H., Dombrowski, F., Willecke, K., Ott, T. Cell Tissue Res. (2002) [Pubmed]
  10. Role of connexin (gap junction) genes in cell growth control: approach with site-directed mutagenesis and dominant-negative effects. Omori, Y., Duflot-Dancer, A., Mesnil, M., Yamasaki, H. Toxicol. Lett. (1998) [Pubmed]
  11. A derivative of oleamide potently inhibits the spontaneous metastasis of mouse melanoma BL6 cells. Ito, A., Morita, N., Miura, D., Koma, Y., Kataoka, T.R., Yamasaki, H., Kitamura, Y., Kita, Y., Nojima, H. Carcinogenesis (2004) [Pubmed]
  12. Connexin 26 enhances the bystander effect in HSVtk/GCV gene therapy for human bladder cancer by adenovirus/PLL/DNA gene delivery. Tanaka, M., Fraizer, G.C., De La Cerda, J., Cristiano, R.J., Liebert, M., Grossman, H.B. Gene Ther. (2001) [Pubmed]
  13. Altered expression of connexins in urethane-induced mouse lung adenomas. Avanzo, J.L., Mesnil, M., Hernandez-Blazquez, F.J., da Silva, T.C., Fukumasu, H., Mori, C.M., Yamasaki, H., Dagli, M.L. Life Sci. (2006) [Pubmed]
  14. Exocrine specific expression of Connexin32 is dependent on the basic helix-loop-helix transcription factor Mist1. Rukstalis, J.M., Kowalik, A., Zhu, L., Lidington, D., Pin, C.L., Konieczny, S.F. J. Cell. Sci. (2003) [Pubmed]
  15. Connexin43 null mice reveal that astrocytes express multiple connexins. Dermietzel, R., Gao, Y., Scemes, E., Vieira, D., Urban, M., Kremer, M., Bennett, M.V., Spray, D.C. Brain Res. Brain Res. Rev. (2000) [Pubmed]
  16. Expression of gap junction proteins connexin 26 and 43 is modulated during differentiation of keratinocytes in newborn mouse epidermis. Kamibayashi, Y., Oyamada, M., Oyamada, Y., Mori, M. J. Invest. Dermatol. (1993) [Pubmed]
  17. Ablation of gap junctional communication in hepatocytes of transgenic mice does not lead to disrupted cellular homeostasis or increased spontaneous tumourigenesis. Ott, T., Jokwitz, M., Lenhard, D., Romualdi, A., Dombrowski, F., Ittrich, C., Schwarz, M., Willecke, K. Eur. J. Cell Biol. (2006) [Pubmed]
  18. Involvement of gap junctions in placental functions and development. Malassiné, A., Cronier, L. Biochim. Biophys. Acta (2005) [Pubmed]
  19. Molecular cloning and functional expression of mouse connexin-30,a gap junction gene highly expressed in adult brain and skin. Dahl, E., Manthey, D., Chen, Y., Schwarz, H.J., Chang, Y.S., Lalley, P.A., Nicholson, B.J., Willecke, K. J. Biol. Chem. (1996) [Pubmed]
  20. Differential regulation of connexin 26 and 43 in murine neocortical precursors. Bittman, K.S., LoTurco, J.J. Cereb. Cortex (1999) [Pubmed]
  21. Altered permeability and modulatory character of connexin channels during mammary gland development. Locke, D., Stein, T., Davies, C., Morris, J., Harris, A.L., Evans, W.H., Monaghan, P., Gusterson, B. Exp. Cell Res. (2004) [Pubmed]
  22. Mouse horizontal cells do not express connexin26 or connexin36. Deans, M.R., Paul, D.L. Cell Commun. Adhes. (2001) [Pubmed]
  23. Altered glucocorticoid receptor expression and function during mouse skin carcinogenesis. Budunova, I.V., Carbajal, S., Kang, H., Viaje, A., Slaga, T.J. Mol. Carcinog. (1997) [Pubmed]
  24. Perturbation in connexin 43 and connexin 26 gap-junction expression in mouse skin hyperplasia and neoplasia. Sawey, M.J., Goldschmidt, M.H., Risek, B., Gilula, N.B., Lo, C.W. Mol. Carcinog. (1996) [Pubmed]
  25. Astrocyte cultures from conditional connexin43-deficient mice. Theis, M., Speidel, D., Willecke, K. Glia (2004) [Pubmed]
  26. Connexin expression in the retina. Söhl, G., Güldenagel, M., Traub, O., Willecke, K. Brain Res. Brain Res. Rev. (2000) [Pubmed]
  27. Expression patterns of connexin genes in mouse retina. Güldenagel, M., Söhl, G., Plum, A., Traub, O., Teubner, B., Weiler, R., Willecke, K. J. Comp. Neurol. (2000) [Pubmed]
  28. Developmental expression and assembly of connexins into homomeric and heteromeric gap junction hemichannels in the mouse mammary gland. Locke, D., Perusinghe, N., Newman, T., Jayatilake, H., Evans, W.H., Monaghan, P. J. Cell. Physiol. (2000) [Pubmed]
  29. A reporter allele for investigating connexin 26 gene expression in the mouse brain. Filippov, M.A., Hormuzdi, S.G., Fuchs, E.C., Monyer, H. Eur. J. Neurosci. (2003) [Pubmed]
 
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