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Gene Review

Gja4  -  gap junction protein, alpha 4

Mus musculus

Synonyms: AU020209, AW558810, Cnx37, Connexin-37, Cx37, ...
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Disease relevance of Gja4


High impact information on Gja4


Biological context of Gja4

  • In fetal ovary, the mRNA transcripts for 3 more connexins (Cx31, Cx37 and Cx45) were expressed in all the genotypes [10].
  • Functional assays of meiotic competence confirm that oocytes from connexin-37-deficient mice are unable to enter M phase (initiate meiotic maturation) unless treated with the phosphatase inhibitor okadaic acid (OA) [11].
  • Unlike growing oocytes from heterozygous control animals, OA-treated oocytes from connexin-37-deficient mice respond acutely and progress rapidly to the circular bivalent stage of meiosis I and upon removal from OA rapidly revert to an interphase state [11].
  • Mice lacking either connexin37 (Cx37) or connexin40 (Cx40), the predominant gap junction proteins present in vascular endothelium, are viable and exhibit phenotypes that are largely non-blood vessel related [12].
  • Of the other six connexin genes which have previously been assigned to a human chromosome, two of these, Cx37 and Cx40, are also found on chromosome 1 [13].

Anatomical context of Gja4


Associations of Gja4 with chemical compounds

  • Cx37 transcripts were also found to increase two to threefold in response to retinoic acid treatment of cultured embryonic carcinoma F9 cells [9].
  • These results support the notion that gap junction hemichannels formed of certain connexins are more likely than others to pair functionally with Cx37, and suggest co-transfection strategies that might prove effective in sensitizing tumor cell populations to GCV [19].
  • In these cells, mouse Cx37 protein was phosphorylated mainly at serine, less at tyrosine, and very little at threonine residues [20].
  • Short-term treatment with simvastatin leads to recovery of Cx37 expression but not Cx40 expression [21].
  • Here we have unambiguously demonstrated that clones K(b)39.5 (39.5) and D122 of 3LL, and C6 and E9 of CMT 64, previously employed, have only normal Cx37 sequences, including those of codon 54 [4].

Co-localisations of Gja4


Regulatory relationships of Gja4


Other interactions of Gja4

  • Differential expression and localisation of connexin-37 and connexin-43 in follicles of different stages in the 4-week-old mouse ovary [18].
  • Other down-regulated genes included: Cyp19a1, Fshr, Inhb, and the oocyte factors Zp1-3 and Gja4 [24].
  • The microvasculature of STZ-induced apoE-deficient mice developed endothelial dysfunction, which may be linked to a decrease in the contribution of the EDHF component due to a decrease in SK2 and 3 and Cx 37 expression [25].
  • Immunostaining revealed that during prenatal development Cx37 predominated in endothelial and endocardial cells but was also detectable in small amounts in the trabeculated and compact layers of ventricular myocardium, as well as in the mesenchyme of conotruncal ridges and atrioventricular cushions [26].
  • H-2K(b)-restricted tumor epitope peptides, including tyrosinase-related protein 2 residues 181-188 (TRP-2) and connexin 37 residues 52-59 (MUT1), were applied to permeability barrier-disrupted C57BL/6 (B6) mouse skin from which the stratum corneum of the epidermis had been removed by tape-stripping [27].

Analytical, diagnostic and therapeutic context of Gja4

  • The purpose of the present study was to localise Cx37 and Cx43 in sections of ovarian mouse follicles of different developmental stage, and compare their relative expression using immunofluorescence and confocal microscopy [18].
  • High stringency hybridization of Northern blots with the coding sequence of Cx40 identified a single transcript of 3.5 kb that is at least 16-fold more abundant in lung-similar to mouse Cx37-than in other adult tissues (kidney, heart, and skin) [28].
  • Continuous Cx37 expression in granulosa cells was confirmed using RT-PCR [29].
  • Comparison of the expression of the principal vascular connexins (Cx37, 40 and 43), implicated in EDHF-mediated dilatation were undertaken by immunohistochemistry [30].


  1. CTL induction by a tumour-associated antigen octapeptide derived from a murine lung carcinoma. Mandelboim, O., Berke, G., Fridkin, M., Feldman, M., Eisenstein, M., Eisenbach, L. Nature (1994) [Pubmed]
  2. Altered pattern of vascular connexin expression in atherosclerotic plaques. Kwak, B.R., Mulhaupt, F., Veillard, N., Gros, D.B., Mach, F. Arterioscler. Thromb. Vasc. Biol. (2002) [Pubmed]
  3. Reduced arteriolar conducted vasoconstriction in septic mouse cremaster muscle is mediated by nNOS-derived NO. McKinnon, R.L., Lidington, D., Bolon, M., Ouellette, Y., Kidder, G.M., Tyml, K. Cardiovasc. Res. (2006) [Pubmed]
  4. Connexin 37 gene is not mutated in lung carcinomas 3LL and CMT. Berke, G., Krutovskikh, V., Yamasaki, H. Cancer Lett. (2003) [Pubmed]
  5. Gap junctional intercellular communication in the mouse ovarian follicle. Goodenough, D.A., Simon, A.M., Paul, D.L. Novartis Found. Symp. (1999) [Pubmed]
  6. Connexin37 protects against atherosclerosis by regulating monocyte adhesion. Wong, C.W., Christen, T., Roth, I., Chadjichristos, C.E., Derouette, J.P., Foglia, B.F., Chanson, M., Goodenough, D.A., Kwak, B.R. Nat. Med. (2006) [Pubmed]
  7. Female infertility in mice lacking connexin 37. Simon, A.M., Goodenough, D.A., Li, E., Paul, D.L. Nature (1997) [Pubmed]
  8. Regression of established murine carcinoma metastases following vaccination with tumour-associated antigen peptides. Mandelboim, O., Vadai, E., Fridkin, M., Katz-Hillel, A., Feldman, M., Berke, G., Eisenbach, L. Nat. Med. (1995) [Pubmed]
  9. Mouse connexin37: cloning and functional expression of a gap junction gene highly expressed in lung. Willecke, K., Heynkes, R., Dahl, E., Stutenkemper, R., Hennemann, H., Jungbluth, S., Suchyna, T., Nicholson, B.J. J. Cell Biol. (1991) [Pubmed]
  10. mRNA expression pattern of multiple members of connexin gene family in normal and abnormal fetal gonads in mouse. Juneja, S.C. Indian J. Physiol. Pharmacol. (2003) [Pubmed]
  11. Oocyte-granulosa cell heterologous gap junctions are required for the coordination of nuclear and cytoplasmic meiotic competence. Carabatsos, M.J., Sellitto, C., Goodenough, D.A., Albertini, D.F. Dev. Biol. (2000) [Pubmed]
  12. Vascular abnormalities in mice lacking the endothelial gap junction proteins connexin37 and connexin40. Simon, A.M., McWhorter, A.R. Dev. Biol. (2002) [Pubmed]
  13. The human lens intrinsic membrane protein MP70 (Cx50) gene: clonal analysis and chromosome mapping. Church, R.L., Wang, J.H., Steele, E. Curr. Eye Res. (1995) [Pubmed]
  14. Expression pattern of connexin gene products at the early developmental stages of the mouse cardiovascular system. Delorme, B., Dahl, E., Jarry-Guichard, T., Briand, J.P., Willecke, K., Gros, D., Théveniau-Ruissy, M. Circ. Res. (1997) [Pubmed]
  15. Connexin expression in the retina. Söhl, G., Güldenagel, M., Traub, O., Willecke, K. Brain Res. Brain Res. Rev. (2000) [Pubmed]
  16. Differential connexin expression in preglomerular and postglomerular vasculature: accentuation during diabetes. Zhang, J., Hill, C.E. Kidney Int. (2005) [Pubmed]
  17. 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]
  18. Differential expression and localisation of connexin-37 and connexin-43 in follicles of different stages in the 4-week-old mouse ovary. Teilmann, S.C. Mol. Cell. Endocrinol. (2005) [Pubmed]
  19. Gap junctions: the "kiss of death" and the "kiss of life". Andrade-Rozental, A.F., Rozental, R., Hopperstad, M.G., Wu, J.K., Vrionis, F.D., Spray, D.C. Brain Res. Brain Res. Rev. (2000) [Pubmed]
  20. Characterization of the gap junction protein connexin37 in murine endothelium, respiratory epithelium, and after transfection in human HeLa cells. Traub, O., Hertlein, B., Kasper, M., Eckert, R., Krisciukaitis, A., Hülser, D., Willecke, K. Eur. J. Cell Biol. (1998) [Pubmed]
  21. Reduced expression of endothelial connexin37 and connexin40 in hyperlipidemic mice: recovery of connexin37 after 7-day simvastatin treatment. Yeh, H.I., Lu, C.S., Wu, Y.J., Chen, C.C., Hong, R.C., Ko, Y.S., Shiao, M.S., Severs, N.J., Tsai, C.H. Arterioscler. Thromb. Vasc. Biol. (2003) [Pubmed]
  22. 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]
  23. Altered dye diffusion and upregulation of connexin37 in mouse aortic endothelium deficient in connexin40. Krüger, O., Bény, J.L., Chabaud, F., Traub, O., Theis, M., Brix, K., Kirchhoff, S., Willecke, K. J. Vasc. Res. (2002) [Pubmed]
  24. Gene expression profiles of cumulus cell oocyte complexes during ovulation reveal cumulus cells express neuronal and immune-related genes: does this expand their role in the ovulation process? Hernandez-Gonzalez, I., Gonzalez-Robayna, I., Shimada, M., Wayne, C.M., Ochsner, S.A., White, L., Richards, J.S. Mol. Endocrinol. (2006) [Pubmed]
  25. Endothelial dysfunction in the streptozotocin-induced diabetic apoE-deficient mouse. Ding, H., Hashem, M., Wiehler, W.B., Lau, W., Martin, J., Reid, J., Triggle, C. Br. J. Pharmacol. (2005) [Pubmed]
  26. Connexin37 in normal and pathological development of mouse heart and great arteries. Haefliger, J.A., Polikar, R., Schnyder, G., Burdet, M., Sutter, E., Pexieder, T., Nicod, P., Meda, P. Dev. Dyn. (2000) [Pubmed]
  27. Percutaneous peptide immunization via corneum barrier-disrupted murine skin for experimental tumor immunoprophylaxis. Seo, N., Tokura, Y., Nishijima, T., Hashizume, H., Furukawa, F., Takigawa, M. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  28. Molecular cloning and functional expression of mouse connexin40, a second gap junction gene preferentially expressed in lung. Hennemann, H., Suchyna, T., Lichtenberg-Fraté, H., Jungbluth, S., Dahl, E., Schwarz, J., Nicholson, B.J., Willecke, K. J. Cell Biol. (1992) [Pubmed]
  29. Selective assembly of connexin37 into heterocellular gap junctions at the oocyte/granulosa cell interface. Veitch, G.I., Gittens, J.E., Shao, Q., Laird, D.W., Kidder, G.M. J. Cell. Sci. (2004) [Pubmed]
  30. The oestrogen receptor {beta} contributes to sex related differences in endothelial function of murine small arteries via EDHF. Luksha, L., Poston, L., Gustafsson, J.A., Hultenby, K., Kublickiene, K. J. Physiol. (Lond.) (2006) [Pubmed]
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