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Gene Review

Gja1  -  gap junction protein, alpha 1

Mus musculus

Synonyms: AU042049, AW546267, Cnx43, Connexin-43, Cx43, ...
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Disease relevance of Gja1


Psychiatry related information on Gja1

  • 1, and Cx43 mRNA levels coincided in most cases and in general corresponded well to the time-response curves for hyperplastic changes in mouse skin [6].

High impact information on Gja1


Chemical compound and disease context of Gja1

  • In conclusion, our results indicate that deletion of one allele of the Cx43 gene clearly favors the carcinogenic effect of urethane administration and results in a higher susceptibility to lung adenoma formation in mice [12].
  • Thus, normal HOSE cells had extensive GJIC and Cx43 expression whereas ovarian carcinoma cells had less and cAMP and retinoic acid did not change these, although both agents inhibited cell growth [13].
  • In the present study, we determined the level of Cx43 mRNA expression in colonic mucosa from normal subjects and subjects with a prior history of colonic polyps or cancer before and after three months of administration of a placebo or beta-carotene [14].
  • Menadione (37 microg/kg i.v.) before 30 minutes coronary occlusion and 2 hour reperfusion reduced infarct size in WT and Cx43+/- mice (24+/-4% versus 24+/-5%) [15].
  • To investigate the phosphorylation state of Cx43, ovarian carcinoma cell lysates were immunoprecipitated and transient tyrosine phosphorylation of Cx43 was detected in ET-1-treated cells [16].

Biological context of Gja1


Anatomical context of Gja1

  • Proteomic analysis of a neoplastic mouse lung epithelial cell line whose tumorigenicity has been abrogated by transfection with the gap junction structural gene for connexin 43, Gja1 [18].
  • However, in the i.v./i.v. embryo, a mutant with randomization of body situs the same pattern of Gja1 asymmetry was found in the limb ectoderm regardless of body situs [19].
  • In the limb bud mesenchyme, Gja1 transcripts were distributed in a posterior distal gradient, coincident with tissue known to have polarizing activity [19].
  • In more proximal regions of the limb where mesenchyme differentiation has been initiated, Gja1 transcripts were expressed only in the outer mesenchymal cells comprising the presumptive perichondrium [19].
  • Therefore, in addition to the reported neural crest cell defect, lack of Cx43 also causes a generalized osteoblast dysfunction, leading to delayed mineralization and skull abnormalities [2].

Associations of Gja1 with chemical compounds

  • Cell to cell diffusion of calcein was poor among Cx43-deficient osteoblasts, whose differentiated phenotypic profile and mineralization potential were greatly impaired, compared with wild-type cells [2].
  • In addition, these Cx43-reintroduced stromal cells showed an increased support ability (3.7-fold) for CAFC-week 1 in normal mouse BM and 5-fold higher supportive ability for CAFC-week 4 in 5-fluorouracil-treated BM cells as compared with Cx43-deficient FL stromal cells [21].
  • Using the doxycycline inducible tet-on system, we generated human malignant trophoblast Jeg3 cells transfected with either Cx40, Cx43, or C-terminal truncated Cx43 (trCx43) [22].
  • Glutathione S-transferase pull-down assay and co-immunoprecipitation demonstrated that CCN3 was able to physically interact with Cx43 [4].
  • Inhibition of gap junctional communication with anandamide in HeLa/Cx43 transfectants substantially restored oscillations (55% of cells) [23].
  • These findings suggest that lowering intracellular redox potential increases the opening of Cx43 and Cx43-EGFP hemichannels, possibly by action on cytoplasmic cysteine residues in the connexin C terminus [24].

Physical interactions of Gja1


Co-localisations of Gja1


Regulatory relationships of Gja1


Other interactions of Gja1


Analytical, diagnostic and therapeutic context of Gja1


  1. Defects in the germ line and gonads of mice lacking connexin43. Juneja, S.C., Barr, K.J., Enders, G.C., Kidder, G.M. Biol. Reprod. (1999) [Pubmed]
  2. Connexin43 deficiency causes delayed ossification, craniofacial abnormalities, and osteoblast dysfunction. Lecanda, F., Warlow, P.M., Sheikh, S., Furlan, F., Steinberg, T.H., Civitelli, R. J. Cell Biol. (2000) [Pubmed]
  3. Endothelin B receptor blockade inhibits dynamics of cell interactions and communications in melanoma cell progression. Bagnato, A., Rosanò, L., Spinella, F., Di Castro, V., Tecce, R., Natali, P.G. Cancer Res. (2004) [Pubmed]
  4. CCN3 (NOV) interacts with connexin43 in C6 glioma cells: possible mechanism of connexin-mediated growth suppression. Fu, C.T., Bechberger, J.F., Ozog, M.A., Perbal, B., Naus, C.C. J. Biol. Chem. (2004) [Pubmed]
  5. 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]
  6. Effect of diverse tumor promoters on the expression of gap-junctional proteins connexin (Cx)26, Cx31.1, and Cx43 in SENCAR mouse epidermis. Budunova, I.V., Carbajal, S., Slaga, T.J. Mol. Carcinog. (1996) [Pubmed]
  7. Cardiac malformation in neonatal mice lacking connexin43. Reaume, A.G., de Sousa, P.A., Kulkarni, S., Langille, B.L., Zhu, D., Davies, T.C., Juneja, S.C., Kidder, G.M., Rossant, J. Science (1995) [Pubmed]
  8. Emerging complexities in identity and function of glial connexins. Theis, M., Söhl, G., Eiberger, J., Willecke, K. Trends Neurosci. (2005) [Pubmed]
  9. G-CSF/SCF reduces inducible arrhythmias in the infarcted heart potentially via increased connexin43 expression and arteriogenesis. Kuhlmann, M.T., Kirchhof, P., Klocke, R., Hasib, L., Stypmann, J., Fabritz, L., Stelljes, M., Tian, W., Zwiener, M., Mueller, M., Kienast, J., Breithardt, G., Nikol, S. J. Exp. Med. (2006) [Pubmed]
  10. Connexin43-dependent mechanism modulates renin secretion and hypertension. Haefliger, J.A., Krattinger, N., Martin, D., Pedrazzini, T., Capponi, A., Döring, B., Plum, A., Charollais, A., Willecke, K., Meda, P. J. Clin. Invest. (2006) [Pubmed]
  11. Connexin 43 mediates spread of Ca2+-dependent proinflammatory responses in lung capillaries. Parthasarathi, K., Ichimura, H., Monma, E., Lindert, J., Quadri, S., Issekutz, A., Bhattacharya, J. J. Clin. Invest. (2006) [Pubmed]
  12. Increased susceptibility to urethane-induced lung tumors in mice with decreased expression of connexin43. Avanzo, J.L., Mesnil, M., Hernandez-Blazquez, F.J., Mackowiak, I.I., Mori, C.M., da Silva, T.C., Oloris, S.C., Gárate, A.P., Massironi, S.M., Yamasaki, H., Dagli, M.L. Carcinogenesis (2004) [Pubmed]
  13. Gap junctional intercellular communication and connexin43 expression in human ovarian surface epithelial cells and ovarian carcinomas in vivo and in vitro. Hanna, E.A., Umhauer, S., Roshong, S.L., Piechocki, M.P., Fernstrom, M.J., Fanning, J.D., Ruch, R.J. Carcinogenesis (1999) [Pubmed]
  14. Expression of mRNA for the gap-junctional protein connexin43 in human colonic tissue is variable in response to beta-carotene supplementation. Frommel, T.O., Lietz, H., Mobarhan, S. Nutrition and cancer. (1994) [Pubmed]
  15. Impairment of diazoxide-induced formation of reactive oxygen species and loss of cardioprotection in connexin 43 deficient mice. Heinzel, F.R., Luo, Y., Li, X., Boengler, K., Buechert, A., García-Dorado, D., Di Lisa, F., Schulz, R., Heusch, G. Circ. Res. (2005) [Pubmed]
  16. Endothelin-1 decreases gap junctional intercellular communication by inducing phosphorylation of connexin 43 in human ovarian carcinoma cells. Spinella, F., Rosanò, L., Di Castro, V., Nicotra, M.R., Natali, P.G., Bagnato, A. J. Biol. Chem. (2003) [Pubmed]
  17. A Gja1 missense mutation in a mouse model of oculodentodigital dysplasia. Flenniken, A.M., Osborne, L.R., Anderson, N., Ciliberti, N., Fleming, C., Gittens, J.E., Gong, X.Q., Kelsey, L.B., Lounsbury, C., Moreno, L., Nieman, B.J., Peterson, K., Qu, D., Roscoe, W., Shao, Q., Tong, D., Veitch, G.I., Voronina, I., Vukobradovic, I., Wood, G.A., Zhu, Y., Zirngibl, R.A., Aubin, J.E., Bai, D., Bruneau, B.G., Grynpas, M., Henderson, J.E., Henkelman, R.M., McKerlie, C., Sled, J.G., Stanford, W.L., Laird, D.W., Kidder, G.M., Adamson, S.L., Rossant, J. Development (2005) [Pubmed]
  18. Proteomic analysis of a neoplastic mouse lung epithelial cell line whose tumorigenicity has been abrogated by transfection with the gap junction structural gene for connexin 43, Gja1. Peebles, K.A., Duncan, M.W., Ruch, R.J., Malkinson, A.M. Carcinogenesis (2003) [Pubmed]
  19. Developmental regulation and asymmetric expression of the gene encoding Cx43 gap junctions in the mouse limb bud. Meyer, R.A., Cohen, M.F., Recalde, S., Zakany, J., Bell, S.M., Scott, W.J., Lo, C.W. Dev. Genet. (1997) [Pubmed]
  20. Connexin43 associated with an N-cadherin-containing multiprotein complex is required for gap junction formation in NIH3T3 cells. Wei, C.J., Francis, R., Xu, X., Lo, C.W. J. Biol. Chem. (2005) [Pubmed]
  21. Connexin-43 gap junctions are involved in multiconnexin-expressing stromal support of hemopoietic progenitors and stem cells. Cancelas, J.A., Koevoet, W.L., de Koning, A.E., Mayen, A.E., Rombouts, E.J., Ploemacher, R.E. Blood (2000) [Pubmed]
  22. Connexin43 interacts with NOV: a possible mechanism for negative regulation of cell growth in choriocarcinoma cells. Gellhaus, A., Dong, X., Propson, S., Maass, K., Klein-Hitpass, L., Kibschull, M., Traub, O., Willecke, K., Perbal, B., Lye, S.J., Winterhager, E. J. Biol. Chem. (2004) [Pubmed]
  23. Gap junctional communication modulates agonist-induced calcium oscillations in transfected HeLa cells. Lin, G.C., Rurangirwa, J.K., Koval, M., Steinberg, T.H. J. Cell. Sci. (2004) [Pubmed]
  24. Opening of connexin 43 hemichannels is increased by lowering intracellular redox potential. Retamal, M.A., Schalper, K.A., Shoji, K.F., Bennett, M.V., Sáez, J.C. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  25. Amino terminal glutamate residues confer spermine sensitivity and affect voltage gating and channel conductance of rat connexin40 gap junctions. Musa, H., Fenn, E., Crye, M., Gemel, J., Beyer, E.C., Veenstra, R.D. J. Physiol. (Lond.) (2004) [Pubmed]
  26. Characterization of the association of connexins and ZO-1 in the lens. Nielsen, P.A., Baruch, A., Giepmans, B.N., Kumar, N.M. Cell Commun. Adhes. (2001) [Pubmed]
  27. Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate. van Zeijl, L., Ponsioen, B., Giepmans, B.N., Ariaens, A., Postma, F.R., Várnai, P., Balla, T., Divecha, N., Jalink, K., Moolenaar, W.H. J. Cell Biol. (2007) [Pubmed]
  28. Distribution of gap junction protein connexin 37 in smooth muscle cells of the rat trachea and pulmonary artery. Nakamura, K., Inai, T., Nakamura, K., Shibata, Y. Arch. Histol. Cytol. (1999) [Pubmed]
  29. Reduced connexin43 expression inhibits atherosclerotic lesion formation in low-density lipoprotein receptor-deficient mice. Kwak, B.R., Veillard, N., Pelli, G., Mulhaupt, F., James, R.W., Chanson, M., Mach, F. Circulation (2003) [Pubmed]
  30. Slow conduction and enhanced anisotropy increase the propensity for ventricular tachyarrhythmias in adult mice with induced deletion of connexin43. van Rijen, H.V., Eckardt, D., Degen, J., Theis, M., Ott, T., Willecke, K., Jongsma, H.J., Opthof, T., de Bakker, J.M. Circulation (2004) [Pubmed]
  31. Tbx2 represses expression of Connexin43 in osteoblastic-like cells. Chen, J.R., Chatterjee, B., Meyer, R., Yu, J.C., Borke, J.L., Isales, C.M., Kirby, M.L., Lo, C.W., Bollag, R.J. Calcif. Tissue Int. (2004) [Pubmed]
  32. Hoxa3 regulates the proliferation and differentiation of the third pharyngeal arch mesenchyme in mice. Chisaka, O., Kameda, Y. Cell Tissue Res. (2005) [Pubmed]
  33. Nkx2.5 homeoprotein regulates expression of gap junction protein connexin 43 and sarcomere organization in postnatal cardiomyocytes. Kasahara, H., Ueyama, T., Wakimoto, H., Liu, M.K., Maguire, C.T., Converso, K.L., Kang, P.M., Manning, W.J., Lawitts, J., Paul, D.L., Berul, C.I., Izumo, S. J. Mol. Cell. Cardiol. (2003) [Pubmed]
  34. Cx43 mediates TGF-beta signaling through competitive Smads binding to microtubules. Dai, P., Nakagami, T., Tanaka, H., Hitomi, T., Takamatsu, T. Mol. Biol. Cell (2007) [Pubmed]
  35. Requirement of a novel gene, Xin, in cardiac morphogenesis. Wang, D.Z., Reiter, R.S., Lin, J.L., Wang, Q., Williams, H.S., Krob, S.L., Schultheiss, T.M., Evans, S., Lin, J.J. Development (1999) [Pubmed]
  36. Drebrin is a novel connexin-43 binding partner that links gap junctions to the submembrane cytoskeleton. Butkevich, E., Hülsmann, S., Wenzel, D., Shirao, T., Duden, R., Majoul, I. Curr. Biol. (2004) [Pubmed]
  37. Replacement by a lacZ reporter gene assigns mouse connexin36, 45 and 43 to distinct cell types in pancreatic islets. Theis, M., Mas, C., Döring, B., Degen, J., Brink, C., Caille, D., Charollais, A., Krüger, O., Plum, A., Nepote, V., Herrera, P., Meda, P., Willecke, K. Exp. Cell Res. (2004) [Pubmed]
  38. Differential connexin expression in preglomerular and postglomerular vasculature: accentuation during diabetes. Zhang, J., Hill, C.E. Kidney Int. (2005) [Pubmed]
  39. Connexin43 and the brain transcriptome of newborn mice. Iacobas, D.A., Iacobas, S., Spray, D.C. Genomics (2007) [Pubmed]
  40. The organization of adherens junctions and desmosomes at the cardiac intercalated disc is independent of gap junctions. Gutstein, D.E., Liu, F.Y., Meyers, M.B., Choo, A., Fishman, G.I. J. Cell. Sci. (2003) [Pubmed]
  41. Analysis of multiple gap junction gene products in the rodent and human mammary gland. Pozzi, A., Risek, B., Kiang, D.T., Gilula, N.B., Kumar, N.M. Exp. Cell Res. (1995) [Pubmed]
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