Gene Symbol: Gja3
Description: gap junction protein, alpha 3
Alias: Cnx46, Cx43, Cx46, Gja-3, gap junction alpha-3 protein, alpha 3 connexin, connexin-46, gap junction membrane channel protein alpha 3
Species: mouse
Products:     Gja3

Top Publications

  1. Chang B, Wang X, Hawes N, Ojakian R, Davisson M, Lo W, et al. A Gja8 (Cx50) point mutation causes an alteration of alpha 3 connexin (Cx46) in semi-dominant cataracts of Lop10 mice. Hum Mol Genet. 2002;11:507-13 pubmed
    ..loss-of-function mutant for alpha 8, as well as a dominant mutation for reducing the phosphorylated forms of alpha 3 connexin in vivo...
  2. Cheng C, Xia C, Li L, White T, Niimi J, Gong X. Gap junction communication influences intercellular protein distribution in the lens. Exp Eye Res. 2008;86:966-74 pubmed publisher
    ..Although the mechanism that drives GFP transport between fiber cells remains unknown, this work reveals that gap junction communication plays a novel role in the regulation of intercellular protein distribution in the lens. ..
  3. White T. Unique and redundant connexin contributions to lens development. Science. 2002;295:319-20 pubmed
    ..Knockout of Cx46 causes a loss of homeostasis and cataracts. Deletion of Cx50 results in reduced ocular growth and cataracts...
  4. Xia C, Liu H, Cheung D, Cheng C, Wang E, Du X, et al. Diverse gap junctions modulate distinct mechanisms for fiber cell formation during lens development and cataractogenesis. Development. 2006;133:2033-40 pubmed
    Different mutations of alpha3 connexin (Cx46 or Gja8) and alpha8 connexin (Cx50 or Gja8), subunits of lens gap junction channels, cause a variety of cataracts via unknown mechanisms...
  5. Gong X, Li E, Klier G, Huang Q, Wu Y, Lei H, et al. Disruption of alpha3 connexin gene leads to proteolysis and cataractogenesis in mice. Cell. 1997;91:833-43 pubmed
    Gap junction channels formed by alpha3 (Cx46) and alpha8 (Cx50) connexin provide pathways for communication between the fiber cells in the normal transparent lens...
  6. Baruch A, Greenbaum D, Levy E, Nielsen P, Gilula N, Kumar N, et al. Defining a link between gap junction communication, proteolysis, and cataract formation. J Biol Chem. 2001;276:28999-9006 pubmed
    Disruption of the connexin alpha 3 (Cx46) gene (alpha 3 (-/-)) in mice results in severe cataracts within the nuclear portion of the lens...
  7. Gong X, Baldo G, Kumar N, Gilula N, Mathias R. Gap junctional coupling in lenses lacking alpha3 connexin. Proc Natl Acad Sci U S A. 1998;95:15303-8 pubmed
    Fiber cells of the lens are interconnected by an extensive network of gap junctions containing alpha3 (Cx46) and alpha8 (Cx50) connexins. A specific role for these connexins in lens homeostasis is not known...
  8. Simon A, Goodenough D. Diverse functions of vertebrate gap junctions. Trends Cell Biol. 1998;8:477-83 pubmed
  9. Xia C, Cheung D, DeRosa A, Chang B, Lo W, White T, et al. Knock-in of alpha3 connexin prevents severe cataracts caused by an alpha8 point mutation. J Cell Sci. 2006;119:2138-44 pubmed
    ..has been previously shown to cause a severe cataract by interacting with endogenous wild-type alpha3 connexin (Cx46) in mouse lenses...

More Information


  1. Xia C, Cheng C, Huang Q, Cheung D, Li L, Dunia I, et al. Absence of alpha3 (Cx46) and alpha8 (Cx50) connexins leads to cataracts by affecting lens inner fiber cells. Exp Eye Res. 2006;83:688-96 pubmed
    ..and transparency have been hypothesized to depend on intercellular gap junction channels, consisting of alpha3 (Cx46) and alpha8 (Cx50) connexin subunits, to transport metabolites, secondary messages and ions between lens cells...
  2. White T, Paul D. Genetic diseases and gene knockouts reveal diverse connexin functions. Annu Rev Physiol. 1999;61:283-310 pubmed
    ..In addition, gene targeting of connexins in mice has provided new insights into connexin function and the significance of connexin diversity. ..
  3. Gong X, Agopian K, Kumar N, Gilula N. Genetic factors influence cataract formation in alpha 3 connexin knockout mice. Dev Genet. 1999;24:27-32 pubmed
    Connexin alpha 3 (Cx46 or Gja3) gene targeted null mice developed lens nuclear cataracts shortly after birth. A large variance in the cataracts was observed in alpha 3 null sibs on a mixed 129SvJae X C57BL/6J F3 background...
  4. Tang Y, Liu X, Zoltoski R, Novak L, Herrera R, Richard I, et al. Age-related cataracts in alpha3Cx46-knockout mice are dependent on a calpain 3 isoform. Invest Ophthalmol Vis Sci. 2007;48:2685-94 pubmed
    ..These results are consistent with the hypothesis that the loss of alpha3Cx46 leads to increased levels of Ca2+ ions, and this increase activates the CAPN3 isoform, Lp82/85, which results in the formation of a nuclear cataract. ..
  5. Martinez Wittinghan F, Sellitto C, Li L, Gong X, Brink P, Mathias R, et al. Dominant cataracts result from incongruous mixing of wild-type lens connexins. J Cell Biol. 2003;161:969-78 pubmed
    ..In the lens, Cx46 and Cx50 provide the gap junctional coupling needed for homeostasis and growth...
  6. Gao J, Sun X, Martinez Wittinghan F, Gong X, White T, Mathias R. Connections between connexins, calcium, and cataracts in the lens. J Gen Physiol. 2004;124:289-300 pubmed
    ..of the present study was to test this calcium circulation hypothesis by studying calcium homeostasis in connexin (Cx46) knockout and (Cx46 for Cx50) knockin mouse lenses, which have different degrees of gap junction coupling...
  7. Ebihara L, Tong J, VERTEL B, White T, Chen T. Properties of connexin 46 hemichannels in dissociated lens fiber cells. Invest Ophthalmol Vis Sci. 2011;52:882-9 pubmed publisher
    To characterize the properties of connexin 46 hemichannels in differentiating fiber cells isolated from mouse lenses. Differentiating fiber cells were isolated from mouse lenses using collagenase...
  8. Ebihara L, Korzyukov Y, Kothari S, Tong J. Cx46 hemichannels contribute to the sodium leak conductance in lens fiber cells. Am J Physiol Cell Physiol. 2014;306:C506-13 pubmed publisher
    ..One of the key components of this system is the sodium leak conductance. Here we investigate the contribution of Cx46 hemichannels to the basal membrane permeability of peripheral fiber cells isolated from transgenic mouse lenses ..
  9. Hsieh C, Kumar N, Gilula N, Francke U. Distribution of genes for gap junction membrane channel proteins on human and mouse chromosomes. Somat Cell Mol Genet. 1991;17:191-200 pubmed
    ..1-q24.1; GJB1 (connexin32) to Xcen-q22; GJB2 (connexin26) to 13; and GJA3 (connexin46) also to 13, probably near GJB2...
  10. Broad T, Lambeth M, Burkin D, Jones C, Pearce P, Maher D, et al. Physical mapping confirms that sheep chromosome 10 has extensive conserved synteny with cattle chromosome 12 and human chromosome 13. Anim Genet. 1996;27:249-53 pubmed
    ..cell hybrids: gap junction protein, beta 2, 26 kDa (connexin 26) (GJB2); gap junction protein, alpha 3, 46 kDa (connexin 46) (GJA3), and esterase D/formylglutathione hydrolase (ESD)...
  11. Mignon C, Fromaget C, Mattei M, Gros D, Yamasaki H, Mesnil M. Assignment of connexin 26 (GJB2) and 46 (GJA3) genes to human chromosome 13q11-->q12 and mouse chromosome 14D1-E1 by in situ hybridization. Cytogenet Cell Genet. 1996;72:185-6 pubmed
  12. Cheng C, Nowak R, Gao J, Sun X, Biswas S, Lo W, et al. Lens ion homeostasis relies on the assembly and/or stability of large connexin 46 gap junction plaques on the broad sides of differentiating fiber cells. Am J Physiol Cell Physiol. 2015;308:C835-47 pubmed publisher
    ..A microcirculation system, facilitated by a network of gap junction channels composed of connexins 46 and 50 (Cx46 and Cx50), is hypothesized to maintain and nourish lens fiber cells...
  13. Rubinos C, Villone K, Mhaske P, White T, Srinivas M. Functional effects of Cx50 mutations associated with congenital cataracts. Am J Physiol Cell Physiol. 2014;306:C212-20 pubmed publisher
    ..However, the mutant did not form functional gap junctions when expressed alone, or with wild-type (WT) Cx46 and Cx50, indicating that V44E is a dominant negative inhibitor of WT connexin function...
  14. Chaible L, Sanches D, Cogliati B, Mennecier G, Dagli M. Delayed osteoblastic differentiation and bone development in Cx43 knockout mice. Toxicol Pathol. 2011;39:1046-55 pubmed publisher
    ..with bone development, namely, osteocalcin, osteopontin, alkaline phosphatase, RUNX2, GJA1, GJC1 (Cx45), and GJA3 (Cx46)...
  15. Tang Y, Crowley T, Kumar N. Global gene expression analysis of lenses from different mouse strains and in the alpha3Cx46 knockout mouse. Mol Vis. 2010;16:113-21 pubmed
    Disruption of the mouse gene encoding the gap junction subunit alpha3 connexin 46 (alpha3Cx46) results in the formation of lens cataracts that have a severity affected by the genetic background of the mouse strain...
  16. Chi N, Bussen M, Brand Arzamendi K, Ding C, Olgin J, Shaw R, et al. Cardiac conduction is required to preserve cardiac chamber morphology. Proc Natl Acad Sci U S A. 2010;107:14662-7 pubmed publisher
    ..By positional cloning, we found that dco encodes Gja3/Cx46, a gap junction protein not previously implicated in heart formation or function...
  17. Li S, Nomata K, Hayashi T, Noguchi M, Kanda S, Kanetake H. Transient decrease in gap junction expression during compensatory renal growth in mice. Urology. 2002;60:726-30 pubmed
    ..The amount of proliferative cell nuclear antigen-positive cells and connexin 43 (Cx43) protein was studied by immunohistochemistry and Western blotting, respectively...
  18. Houghton F, Barr K, Walter G, Gabriel H, Grummer R, Traub O, et al. Functional significance of gap junctional coupling in preimplantation development. Biol Reprod. 2002;66:1403-12 pubmed
    ..New evidence of this diversification is presented using rat blastocyst outgrowths. ..
  19. Yamasaki H, Krutovskikh V, Mesnil M, Tanaka T, Zaidan Dagli M, Omori Y. Role of connexin (gap junction) genes in cell growth control and carcinogenesis. C R Acad Sci III. 1999;322:151-9 pubmed
    ..We have produced various dominant-negative mutants of Cx26, Cx32 and Cx43 and showed that some of them prevent the growth control exerted by the corresponding wild-type genes...
  20. Lo C. Genes, gene knockouts, and mutations in the analysis of gap junctions. Dev Genet. 1999;24:1-4 pubmed
    ..It may be timely to form a Nomenclature Committee to establish a uniform classification scheme for naming gap junction proteins. ..
  21. Pelletier R, Akpovi C, Chen L, Kumar N, Vitale M. Complementary expression and phosphorylation of Cx46 and Cx50 during development and following gene deletion in mouse and in normal and orchitic mink testes. Am J Physiol Regul Integr Comp Physiol. 2015;309:R255-76 pubmed publisher
    ..This report assesses mechanisms underlying the regulation of connexin 46 (Cx46) and Cx50 in mouse testis and those accompanying a "natural" seasonal and a pathological arrest of ..
  22. Gibson L, Holmgreen S, Huang D, Bernard O, Copeland N, Jenkins N, et al. bcl-w, a novel member of the bcl-2 family, promotes cell survival. Oncogene. 1996;13:665-75 pubmed
    ..These findings suggest that bcl-w participates in the control of apoptosis in multiple cell types. Its functional similarity to bcl-2 also makes it an attractive candidate proto-oncogene. ..
  23. Berthoud V, Minogue P, Yu H, Snabb J, Beyer E. Connexin46fs380 causes progressive cataracts. Invest Ophthalmol Vis Sci. 2014;55:6639-48 pubmed publisher
    Although many connexin46 (Cx46) mutants have been linked to inherited human cataracts, there are no adequate animal models for their study...
  24. Maddala R, Nagendran T, de Ridder G, Schey K, Rao P. L-type calcium channels play a critical role in maintaining lens transparency by regulating phosphorylation of aquaporin-0 and myosin light chain and expression of connexins. PLoS ONE. 2013;8:e64676 pubmed publisher
  25. Slavi N, Rubinos C, Li L, Sellitto C, White T, Mathias R, et al. Connexin 46 (cx46) gap junctions provide a pathway for the delivery of glutathione to the lens nucleus. J Biol Chem. 2014;289:32694-702 pubmed publisher
    ..Using electrophysiological measurements, we found that channels formed by Cx46 and Cx50, the two connexin isoforms expressed in the lens, were moderately cation-selective (P(Na)/P(Cl) ∼5 ..
  26. Schwarz H, Chang Y, Hennemann H, Dahl E, Lalley P, Willecke K. Chromosomal assignments of mouse connexin genes, coding for gap junctional proteins, by somatic cell hybridization. Somat Cell Mol Genet. 1992;18:351-9 pubmed
    ..In addition, our results confirm the recent assignment of mouse connexin genes Cx26, Cx32, Cx37, Cx40, Cx43, and Cx46 to mouse chromosomes 14, X, 4, 3, 10, and 14, respectively, by analysis of interspecific backcrosses and by somatic ..
  27. Wang E, Geng A, Maniar A, Mui B, Gong X. Connexin 50 Regulates Surface Ball-and-Socket Structures and Fiber Cell Organization. Invest Ophthalmol Vis Sci. 2016;57:3039-46 pubmed publisher
    ..Moreover, only small gap junction plaques consisting of Cx46 (?3 connexin) were detected in cortical fibers and the distributions of the BS-associated beta-dystroglycan and ZO-..
  28. Hoang Q, Qian H, Ripps H. Functional analysis of hemichannels and gap-junctional channels formed by connexins 43 and 46. Mol Vis. 2010;16:1343-52 pubmed
    ..Retinal pigment epithelium (RPE) cells express Cx43 and Cx46...
  29. Dunia I, Cibert C, Gong X, Xia C, Recouvreur M, Levy E, et al. Structural and immunocytochemical alterations in eye lens fiber cells from Cx46 and Cx50 knockout mice. Eur J Cell Biol. 2006;85:729-52 pubmed
    In the current study we describe the changes of overall organization of lens fiber cells in connexin 46 (Cx46) and connexin 50 (Cx50) knockout mice...
  30. Anderson C, Zundel M, Werner R. Variable promoter usage and alternative splicing in five mouse connexin genes. Genomics. 2005;85:238-44 pubmed
    ..cDNA targeting five candidate genes, Cx31, Cx40, Cx45, Cx46, and Cx47 (approved gene symbols Gjb3, Gja5, Gja7, Gja3, and Gja12, respectively), revealed the existence of multiple previously unknown exons upstream of the coding ..
  31. Juneja S. mRNA expression pattern of multiple members of connexin gene family in normal and abnormal fetal gonads in mouse. Indian J Physiol Pharmacol. 2003;47:147-56 pubmed
    ..Gap junctions play important roles in ovarian and testicular function. Connexin 43 (Cx43) knockout mouse is a model for developmentally impaired fetal gonads...
  32. Sohl G, Willecke K. An update on connexin genes and their nomenclature in mouse and man. Cell Commun Adhes. 2003;10:173-80 pubmed
    ..Furthermore, this short review contains an update on phenotypic correlations between connexin deficient mice and patients bearing mutations in their orthologous connexin genes. ..
  33. Nielsen P, Baruch A, Shestopalov V, Giepmans B, Dunia I, Benedetti E, et al. Lens connexins alpha3Cx46 and alpha8Cx50 interact with zonula occludens protein-1 (ZO-1). Mol Biol Cell. 2003;14:2470-81 pubmed
    ..The spatial variation in the interaction of ZO-1 with lens gap junctions is intriguing and is suggestive of multiple dynamic roles for this association. ..
  34. Davies T, Barr K, Jones D, Zhu D, Kidder G. Multiple members of the connexin gene family participate in preimplantation development of the mouse. Dev Genet. 1996;18:234-43 pubmed
    ..They can be divided into two groups with respect to the timing of mRNA accumulation: Cx31, Cx43, and Cx45 mRNAs accumulate continuously from the two- or four-cell stage, whereas Cx30.3, Cx31...
  35. Xia C, Chang B, DeRosa A, Cheng C, White T, Gong X. Cataracts and microphthalmia caused by a Gja8 mutation in extracellular loop 2. PLoS ONE. 2012;7:e52894 pubmed publisher
    ..Immunohistological data reveal that Cx50-R205G mutant proteins and endogenous wild-type Cx46 (or ?3 connexin) proteins form diffuse tiny spots rather than typical punctate signals of normal gap junctions in ..
  36. von Maltzahn J, Euwens C, Willecke K, Sohl G. The novel mouse connexin39 gene is expressed in developing striated muscle fibers. J Cell Sci. 2004;117:5381-92 pubmed
    ..As expression of no other known connexin could be verified in these cells, intercellular dye transfer might result from functional expression of Cx39 in developing striated muscle fibers. ..
  37. Buniello A, Montanaro D, Volinia S, Gasparini P, Marigo V. An expression atlas of connexin genes in the mouse. Genomics. 2004;83:812-20 pubmed
  38. Forge A, Becker D, Casalotti S, Edwards J, Marziano N, Nevill G. Gap junctions in the inner ear: comparison of distribution patterns in different vertebrates and assessement of connexin composition in mammals. J Comp Neurol. 2003;467:207-31 pubmed
    ..ear by RT-PCR, Western blotting, and immunohistochemistry revealed four connexin isotypes, cx26, cx30, cx31, and cx43, in the cochlea and three, cx26, cx30, and cx43, in the vestibular organs...
  39. Gao Y, Spray D. Structural changes in lenses of mice lacking the gap junction protein connexin43. Invest Ophthalmol Vis Sci. 1998;39:1198-209 pubmed
    To investigate the role of the gap junction protein connexin43 (Cx43), which is predominantly expressed in lens epithelial cells in the control of lens development and organization...