Gja5

Summary

Gene Symbol: Gja5
Description: gap junction protein, alpha 5
Alias: 5730555N10Rik, Cnx40, Cx40, Gja-5, gap junction alpha-5 protein, connexin-40, gap junction membrane channel protein alpha 5
Species: mouse

Top Publications

  1. ncbi Expression pattern of connexin gene products at the early developmental stages of the mouse cardiovascular system
    B Delorme
    Laboratoire de Genetique et Physiologie du Developpement, UMR C9943, Institut de Biologie du Developpement de Marseille, France
    Circ Res 81:423-37. 1997
  2. ncbi Mice lacking connexin40 have cardiac conduction abnormalities characteristic of atrioventricular block and bundle branch block
    A M Simon
    Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Curr Biol 8:295-8. 1998
  3. ncbi Loss of connexin45 causes a cushion defect in early cardiogenesis
    M Kumai
    Department of Developmental Molecular Anatomy, Graduate School of Medical Science, Kyushu University, Fukuoka 812 8582, Japan
    Development 127:3501-12. 2000
  4. ncbi Patterning the embryonic heart: identification of five mouse Iroquois homeobox genes in the developing heart
    V M Christoffels
    Experimental and Molecular Cardiology Group, University of Amsterdam, The Netherlands
    Dev Biol 224:263-74. 2000
  5. ncbi Abnormal cardiac conduction and morphogenesis in connexin40 and connexin43 double-deficient mice
    S Kirchhoff
    Universitat Bonn, Institut fur Genetik, Abt Molekulargenetik, Bonn, Germany
    Circ Res 87:399-405. 2000
  6. ncbi Null mutation of connexin43 causes slow propagation of ventricular activation in the late stages of mouse embryonic development
    D Vaidya
    Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, USA
    Circ Res 88:1196-202. 2001
  7. ncbi A murine model of Holt-Oram syndrome defines roles of the T-box transcription factor Tbx5 in cardiogenesis and disease
    B G Bruneau
    Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    Cell 106:709-21. 2001
  8. ncbi Vascular abnormalities in mice lacking the endothelial gap junction proteins connexin37 and connexin40
    Alexander M Simon
    Department of Physiology, University of Arizona, Tucson, 85724, USA
    Dev Biol 251:206-20. 2002
  9. ncbi Comparison of connexin expression patterns in the developing mouse heart and human foetal heart
    Steven R Coppen
    Cardiac Medicine, National Heart and Lung Institute, Faculty of Medicine, Imperial College, Royal Brompton Hospital, London, UK
    Mol Cell Biochem 242:121-7. 2003
  10. ncbi Spatiotemporal pattern of commitment to slowed proliferation in the embryonic mouse heart indicates progressive differentiation of the cardiac conduction system
    David Sedmera
    Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    Anat Rec A Discov Mol Cell Evol Biol 274:773-7. 2003

Research Grants

  1. Gap Junction Mediated Signaling and Vascular Responses
    Alexander M Simon; Fiscal Year: 2010
  2. CONTROL OF CONNEXIN TRANSPORT AND ASSEMBLY
    Michael Koval; Fiscal Year: 2004
  3. INTERCELLULAR COMMUNICATION IN MICROVESSELS
    Brian Duling; Fiscal Year: 2004
  4. Regulation of the Endothelial Cell Glycocalyx
    Brian Duling; Fiscal Year: 2008
  5. Molecular determinants of lung barrier function
    Michael Koval; Fiscal Year: 2009

Scientific Experts

Detail Information

Publications142 found, 100 shown here

  1. ncbi Expression pattern of connexin gene products at the early developmental stages of the mouse cardiovascular system
    B Delorme
    Laboratoire de Genetique et Physiologie du Developpement, UMR C9943, Institut de Biologie du Developpement de Marseille, France
    Circ Res 81:423-37. 1997
    ..Products of several Cx genes have been identified in the mammalian heart (eg, Cx45, Cx43, Cx40, and Cx37), and their expression was shown to be regulated during the development of the myocardium...
  2. ncbi Mice lacking connexin40 have cardiac conduction abnormalities characteristic of atrioventricular block and bundle branch block
    A M Simon
    Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Curr Biol 8:295-8. 1998
    ..the expression of connexins - the family of proteins from which gap junctions are formed - reveal that connexin40 (Cx40) is prominent in the conduction system [4]...
  3. ncbi Loss of connexin45 causes a cushion defect in early cardiogenesis
    M Kumai
    Department of Developmental Molecular Anatomy, Graduate School of Medical Science, Kyushu University, Fukuoka 812 8582, Japan
    Development 127:3501-12. 2000
    ..These results indicate a requirement for gap junction channels during early cardiogenesis and hence implicate connexin45 in congenital heart diseases. http://www. biologists.com/Development/movies/dev4369.html..
  4. ncbi Patterning the embryonic heart: identification of five mouse Iroquois homeobox genes in the developing heart
    V M Christoffels
    Experimental and Molecular Cardiology Group, University of Amsterdam, The Netherlands
    Dev Biol 224:263-74. 2000
    ....
  5. ncbi Abnormal cardiac conduction and morphogenesis in connexin40 and connexin43 double-deficient mice
    S Kirchhoff
    Universitat Bonn, Institut fur Genetik, Abt Molekulargenetik, Bonn, Germany
    Circ Res 87:399-405. 2000
    Connexin40-deficient (Cx40(-/-)/Cx43(+/+)) and connexin43-heterozygous knockout mice (Cx40(+/+)/Cx43(+/-)) are viable but show cardiac conduction abnormalities...
  6. ncbi Null mutation of connexin43 causes slow propagation of ventricular activation in the late stages of mouse embryonic development
    D Vaidya
    Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, USA
    Circ Res 88:1196-202. 2001
    ..3 [7.8 to 8.9], and Cx43(-/-) 1.7 [1.3 to 2.1; P<0.005]) corresponding with the downregulation of Cx40. Cx40 and Cx45 mRNAs were detectable in ventricular homogenates even at 17...
  7. ncbi A murine model of Holt-Oram syndrome defines roles of the T-box transcription factor Tbx5 in cardiogenesis and disease
    B G Bruneau
    Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    Cell 106:709-21. 2001
    ..Surprisingly, Tbx5 haploinsufficiency also markedly decreased atrial natriuretic factor (ANF) and connexin 40 (cx40) transcription, implicating these as Tbx5 target genes and providing a mechanism by which 50% reduction ..
  8. ncbi Vascular abnormalities in mice lacking the endothelial gap junction proteins connexin37 and connexin40
    Alexander M Simon
    Department of Physiology, University of Arizona, Tucson, 85724, USA
    Dev Biol 251:206-20. 2002
    ..Mice lacking either connexin37 (Cx37) or connexin40 (Cx40), the predominant gap junction proteins present in vascular endothelium, are viable and exhibit phenotypes that are ..
  9. ncbi Comparison of connexin expression patterns in the developing mouse heart and human foetal heart
    Steven R Coppen
    Cardiac Medicine, National Heart and Lung Institute, Faculty of Medicine, Imperial College, Royal Brompton Hospital, London, UK
    Mol Cell Biochem 242:121-7. 2003
    ..The expression of the three major connexins (Cx43, Cx40 and Cx45) present in cardiac myocytes is known to be developmentally regulated but it is not clear how the patterns ..
  10. ncbi Spatiotemporal pattern of commitment to slowed proliferation in the embryonic mouse heart indicates progressive differentiation of the cardiac conduction system
    David Sedmera
    Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    Anat Rec A Discov Mol Cell Evol Biol 274:773-7. 2003
    ..5-13.5. These patterns of slowed proliferation correlate well with those in other species, and can serve as a useful marker for the forming conduction system...
  11. ncbi Architectural and functional asymmetry of the His-Purkinje system of the murine heart
    Lucile Miquerol
    Laboratoire de Genetique et Physiologie du Developpement, UMR 6545, Institut de Biologie du Developpement de Marseille, Universite de la Mediterranee, France
    Cardiovasc Res 63:77-86. 2004
    ..The aim of this work was to target a vital reporter gene in the mouse cardiac conduction system (CS) to distinguish this tissue from the surrounding myocardium in the adult heart...
  12. ncbi Cooperative and antagonistic interactions between Sall4 and Tbx5 pattern the mouse limb and heart
    Kazuko Koshiba-Takeuchi
    Programs in Cardiovascular Research, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada
    Nat Genet 38:175-83. 2006
    ..Thus, a positive and negative feed-forward circuit between Tbx5 and Sall4 ensures precise patterning of embryonic limb and heart and provides a unifying mechanism for heart/hand syndromes...
  13. ncbi Formation of the venous pole of the heart from an Nkx2-5-negative precursor population requires Tbx18
    Vincent M Christoffels
    Department of Experimental and Molecular Cardiology Group, Academic Medical Center, Amsterdam, The Netherlands
    Circ Res 98:1555-63. 2006
    ....
  14. ncbi Molecular pathway for the localized formation of the sinoatrial node
    Mathilda T M Mommersteeg
    Center for Heart Failure Research, Academic Medical Centre, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands
    Circ Res 100:354-62. 2007
    ....
  15. ncbi Targeted mutation reveals essential functions of the homeodomain transcription factor Shox2 in sinoatrial and pacemaking development
    Rudiger J Blaschke
    Human Genetics, University of Heidelberg, Heidelberg, Germany
    Circulation 115:1830-8. 2007
    ..Here, we report on a highly restricted expression pattern of the homeodomain transcription factor Shox2 in the sinus venosus myocardium, including the sinoatrial nodal region and the venous valves...
  16. pmc Connexin37 and Connexin43 deficiencies in mice disrupt lymphatic valve development and result in lymphatic disorders including lymphedema and chylothorax
    John D Kanady
    Department of Physiology, University of Arizona, Tucson, AZ 85724, USA
    Dev Biol 354:253-66. 2011
    ..These results show that at least three Cxs are expressed in the developing lymphatic vasculature and, when defective, are associated with clinically manifest lymphatic disorders in mice and man...
  17. doi The effect of connexin40 deficiency on ventricular conduction system function during development
    Barbora Sankova
    Department of Cardiovascular Morphogenesis, Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska 1083, 14220 Prague, Czech Republic
    Cardiovasc Res 95:469-79. 2012
    ..The aim of this study was to characterize ventricular activation patterns in normal and connexin40-deficient mice in order to dissect the role of connexin40 in developing the conduction system...
  18. doi Tissue distribution and subcellular localization of the cardiac sodium channel during mouse heart development
    Jorge N Domínguez
    Department of Experimental Biology, Faculty of Experimental Sciences, University of Jaen, Paraje de las Lagunillas, S N, Jaén 23071, Spain
    Cardiovasc Res 78:45-52. 2008
    ..The aim of this study was to analyse the mRNA expression levels and protein distribution of the cardiac sodium channel Scn5a/Nav1.5 during mouse cardiogenesis...
  19. ncbi Differential expression of the gap junction proteins connexin45, -43, -40, -31, and -26 in mouse skin
    A Butterweck
    Abt Molekulargenetik der Universität, Bonn Germany
    Eur J Cell Biol 65:152-63. 1994
    ..and -31 were located similarly as in embryonic tissue, but Cx45 as well as Cx26 were not detected and in addition Cx40 was weakly expressed in the stratum basale...
  20. ncbi Impaired conduction of vasodilation along arterioles in connexin40-deficient mice
    C de Wit
    Physiologisches Institut, Ludwig Maximilians Universitat Munchen, Munchen, Germany
    Circ Res 86:649-55. 2000
    ..transmission of vasomotor responses in the intact skeletal muscle microcirculation of connexin40-deficient mice (Cx40(-/-))...
  21. ncbi Comparison of connexin 43, 40 and 45 expression patterns in the developing human and mouse hearts
    R A Kaba
    Cardiac Medicine, National Heart and Lung Institute, Imperial College, London, United Kingdom
    Cell Commun Adhes 8:339-43. 2001
    ..In general, these dynamic changes of connexins 43, 40 and 45 during mouse cardiac development appear to be mirrored in the human...
  22. pmc Essential roles of the bHLH transcription factor Hrt2 in repression of atrial gene expression and maintenance of postnatal cardiac function
    Mei Xin
    Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 104:7975-80. 2007
    ..These findings reveal a ventricular myocardial cell-autonomous function for Hrt2 in the suppression of atrial cell identity and the maintenance of postnatal cardiac function...
  23. doi Increased expression of renal cyclooxygenase-2 and neuronal nitric oxide synthase in hypertensive Cx40-deficient mice
    Nathalie Krattinger
    Department of Medicine, University Hospital, Lausanne, Switzerland
    J Vasc Res 46:188-98. 2009
    b>Cx40-deficient mice (Cx40-/-) are hypertensive due to increased renin secretion. We evaluated the renal expression of neuronal nitric oxide synthase (nNOS) and cyclooxygenases COX-1 and COX-2, three macula densa enzymes...
  24. pmc Connexin expression in renin-producing cells
    Lisa Kurtz
    Institute of Physiology, University of Regensburg, Regensburg, Germany
    J Am Soc Nephrol 20:506-12. 2009
    Absence of connexin 40 (Cx40) leads to ectopic juxtaglomerular renin expression and abrogates recruitment of renin-expressing cells in the adult kidney but does not disturb renin expression during kidney development...
  25. doi Mutations in the NOTCH pathway regulator MIB1 cause left ventricular noncompaction cardiomyopathy
    Guillermo Luxan
    Program of Cardiovascular Developmental Biology, Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain
    Nat Med 19:193-201. 2013
    ..These results implicate NOTCH signaling in LVNC and indicate that MIB1 mutations arrest chamber myocardium development, preventing trabecular maturation and compaction...
  26. pmc The short stature homeobox 2 (Shox2)-bone morphogenetic protein (BMP) pathway regulates dorsal mesenchymal protrusion development and its temporary function as a pacemaker during cardiogenesis
    Cheng Sun
    From the Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana 70118
    J Biol Chem 290:2007-23. 2015
    ..to increased apoptosis, accompanied by dramatically reduced expression of Bmp4 and Hcn4, ectopic activation of Cx40, and an aberrant pattern of action potentials...
  27. ncbi Genetic diseases and gene knockouts reveal diverse connexin functions
    T W White
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Annu Rev Physiol 61:283-310. 1999
    ..In addition, gene targeting of connexins in mice has provided new insights into connexin function and the significance of connexin diversity...
  28. ncbi Connexin40-deficient mice exhibit atrioventricular nodal and infra-Hisian conduction abnormalities
    B A VanderBrink
    Cardiac Arrhythmia Service, New England Medical Center, Boston, Massachusetts 02111, USA
    J Cardiovasc Electrophysiol 11:1270-6. 2000
    Previous electrophysiologic investigations have described AV conduction disturbances in connexin40 (Cx40)-deficient mice...
  29. ncbi Altered dye diffusion and upregulation of connexin37 in mouse aortic endothelium deficient in connexin40
    Olaf Krüger
    Institut fur Genetik, Abteilung Molekulargenetik, Universitat Bonn, Deutschland
    J Vasc Res 39:160-72. 2002
    Connexin40 (Cx40), connexin37 (Cx37) and connexin43 (Cx43) are subunit proteins of gap junction channels in the vascular wall which are presumably involved in the propagation of vasomotor signals...
  30. ncbi The transcriptional repressor Tbx3 delineates the developing central conduction system of the heart
    Willem M H Hoogaars
    Experimental and Molecular Cardiology Group, AMC, University of Amsterdam, Amsterdam, The Netherlands
    Cardiovasc Res 62:489-99. 2004
    ..We studied the developmental expression pattern and functional aspects of the T-box transcription factor Tbx3, a novel marker for the murine central conduction system (CCS)...
  31. ncbi Temporal and spatial expression pattern of beta1 sodium channel subunit during heart development
    Jorge N Domínguez
    Department of Experimental Biology, Faculty of Experimental Sciences, University of Jaen, Paraje de las Lagunillas, S N, 23071 Jaen, Spain
    Cardiovasc Res 65:842-50. 2005
    ..The aim of this study is to analyze Scn1b mRNA expression levels and protein distribution of Scn1b, a putative modulator of the pore-forming Na(+) channel subunit in the heart, during mouse cardiac development...
  32. ncbi Connexin40 and connexin43 in mouse aortic endothelium: evidence for coordinated regulation
    Brant E Isakson
    Department of Molecular Physiology and Biological Physics, Robert M Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA
    Am J Physiol Heart Circ Physiol 290:H1199-205. 2006
    ..To reveal a possible interaction between connexin40 (Cx40) and connexin43 (Cx43) in endothelium, we studied their distribution in vessels from C57Bl/6 and Cx40 knockout mice ..
  33. pmc Reduced gap junctional coupling leads to uncorrelated motor neuron firing and precocious neuromuscular synapse elimination
    Kirkwood E Personius
    Department of Rehabilitation Science, School of Public Health and Health Professions, University at Buffalo, The State University of New York, Buffalo, NY 14214 3079, USA
    Proc Natl Acad Sci U S A 104:11808-13. 2007
    ..motor neuron activity that, in turn, modulates neuromuscular synapse elimination, by using mutant mice lacking connexin 40 (Cx40), a developmentally regulated gap junction protein expressed in motor and other spinal neurons...
  34. pmc Robo4 stabilizes the vascular network by inhibiting pathologic angiogenesis and endothelial hyperpermeability
    Christopher A Jones
    Department of Oncological Sciences, University of Utah, 15 North 2030 East, Salt Lake City, Utah 84112, USA
    Nat Med 14:448-53. 2008
    ....
  35. pmc Downregulation of connexin40 is associated with coronary endothelial cell dysfunction in streptozotocin-induced diabetic mice
    Ayako Makino
    Division of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, CA 92093 0618, USA
    Am J Physiol Cell Physiol 295:C221-30. 2008
    ..Coronary ECs isolated from diabetic mice exhibit lowered protein levels of Cx37 and Cx40 (but not Cx43) and a loss of gap junction intercellular communication (GJIC)...
  36. doi The del22q11.2 candidate gene Tbx1 controls regional outflow tract identity and coronary artery patterning
    Magali Théveniau-Ruissy
    Developmental Biology Institute of Marseilles Luminy, Inserm Avenir Group, UMR 6216 CNRS Université de la Méditerrané, Campus de Luminy, Marseille Cedex 9, France
    Circ Res 103:142-8. 2008
    ..Our results implicate second heart field development in coronary artery patterning and provide new insights into the association between conotruncal defects and coronary artery anomalies...
  37. doi Connexin 30 is expressed in the mouse sino-atrial node and modulates heart rate
    Daniel Gros
    Institut de Biologie du Developpement de Marseille Luminy, Universite de la Mediterranee, Marseille, France
    Cardiovasc Res 85:45-55. 2010
    ..This study aimed at characterizing expression and the functional role of the Gjb6 gene, encoding for connexin 30 (Cx30) protein, in the adult mouse heart...
  38. doi Neuregulin 1 sustains the gene regulatory network in both trabecular and nontrabecular myocardium
    Donna Lai
    Victor Chang Cardiac Research Institute, Lowy Packer Building, 405 Liverpool St, Darlinghurst 2010, Australia
    Circ Res 107:715-27. 2010
    ..In development, the membrane-tethered signaling ligand Neuregulin (Nrg)1, expressed in endocardium, is essential for ventricular morphogenesis. In adults, Nrg1 protects against heart failure and can induce cardiomyocytes to divide...
  39. doi Loss of connexin40 is associated with decreased endothelium-dependent relaxations and eNOS levels in the mouse aorta
    Florian Alonso
    Service of Internal Medicine, Laboratory of Experimental Medicine 19 135S, University Hospital, CHUV, Lausanne, Switzerland
    Am J Physiol Heart Circ Physiol 299:H1365-73. 2010
    ..Endothelial cells of mouse aorta are interconnected by gap junctions made of connexin40 (Cx40) and connexin37 (Cx37), allowing the exchange of signaling molecules to coordinate their activity...
  40. pmc Remodeling of the peripheral cardiac conduction system in response to pressure overload
    Brett S Harris
    Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    Am J Physiol Heart Circ Physiol 302:H1712-25. 2012
    ..PCS cardiomyocytes showed a 98% increase in the number of Cx40-positive gap junction particles, with an associated twofold increase in gene expression (P < 0.05)...
  41. pmc Dll4-Notch signaling determines the formation of native arterial collateral networks and arterial function in mouse ischemia models
    Brunella Cristofaro
    CIRB College de France, Inserm U1050 CNRS UMR 7241, Paris, France
    Development 140:1720-9. 2013
    ....
  42. doi Functional suppression of Kcnq1 leads to early sodium channel remodelling and cardiac conduction system dysmorphogenesis
    Angel J De La Rosa
    Department of Experimental Biology, Faculty of Experimental Sciences, University of Jaen, Paraje de Lagunillas, S N, Jaén 23071, Spain
    Cardiovasc Res 98:504-14. 2013
    ....
  43. doi The Connexin40A96S mutation from a patient with atrial fibrillation causes decreased atrial conduction velocities and sustained episodes of induced atrial fibrillation in mice
    Indra Lübkemeier
    Life and Medical Sciences LIMES Institute, Molecular Genetics, University of Bonn, Bonn, Germany
    J Mol Cell Cardiol 65:19-32. 2013
    ..In the mammalian heart the gap junction proteins connexin40 (Cx40) and connexin43 (Cx43) are strongly expressed in the atrial myocardium mediating effective propagation of ..
  44. pmc Cardiac arrhythmia induced by genetic silencing of 'funny' (f) channels is rescued by GIRK4 inactivation
    Pietro Mesirca
    1 Département de Physiologie, Institut de Genomique Fonctionnelle, LabEx ICST, F 34094 Montpellier, France 2 UMR 5203, Centre National de la Recherche Scientifique, Universités de Montpellier 1 and 2, F 34094 Montpellier, France 3 INSERM U661, Universités de Montpellier 1 and 2, F 34094 Montpellier, France
    Nat Commun 5:4664. 2014
    ....
  45. doi Inducible deletion of connexin 40 in adult mice causes hypertension and disrupts pressure control of renin secretion
    Melanie Gerl
    Department of Physiology, University of Regensburg, Regensburg, Germany
    Kidney Int 87:557-63. 2015
    Genetic loss-of-function defects of connexin 40 in renal juxtaglomerular cells are associated with renin-dependent hypertension...
  46. doi Wnt4 is essential to normal mammalian lung development
    Arianna Caprioli
    Dept of Biology and Physical Sciences, Marymount Univ, 2807 N Glebe Rd, Arlington, VA 22207, USA
    Dev Biol 406:222-34. 2015
    ..Together, these data reveal a previously unknown role for the secreted protein Wnt4 in respiratory system development. ..
  47. doi Interaction Between ALK1 Signaling and Connexin40 in the Development of Arteriovenous Malformations
    Konstantinos Gkatzis
    From the Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands K G, C L M CNRS Unité mixte de recherche 7241 INSERM U1050, Center for Interdisciplinary Research in Biology, College de France, Paris Cedex 05, France J T, D D S L, S M, N L, F L MEMOLIFE Laboratory of Excellence, Paris Sciences et Lettres Research University, Paris, France J T, D D S L, S M, N L, F L Department of Radiology, AP HP, Tenon Hospital, Paris, France M F C Sorbonne Universités, UPMC University, Paris, France M F C St Antonius Hospital, Nieuwegein, The Netherlands F D, R J S, C J W, J J M Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville S P O Aix Marseille Université, CNRS IBDM UMR 7288, NJ 08543
    Arterioscler Thromb Vasc Biol 36:707-17. 2016
    To determine the role of Gja5 that encodes for the gap junction protein connexin40 in the generation of arteriovenous malformations in the hereditary hemorrhagic telangiectasia type 2 (HHT2) mouse model.
  48. doi A novel conditional mouse model for Nkx2-5 reveals transcriptional regulation of cardiac ion channels
    Milena B Furtado
    Australian Regenerative Medicine Institute, Monash University, Clayton, VIC 3800, Australia The Jackson Laboratory, ME 04609, United States
    Differentiation 91:29-41. 2016
    ....
  49. pmc Segregated Foxc2, NFATc1 and Connexin expression at normal developing venous valves, and Connexin-specific differences in the valve phenotypes of Cx37, Cx43, and Cx47 knockout mice
    Stephanie J Munger
    Department of Physiology, University of Arizona, Tucson, AZ 85724, USA Electronic address
    Dev Biol 412:173-90. 2016
    ..The partition of Foxc2 and NFATc1 expression at VV leaflets makes it unlikely that these factors directly cooperate during the leaflet elongation stage of VV development. ..
  50. pmc Pitx2 confers left morphological, molecular, and functional identity to the sinus venosus myocardium
    Grazia Ammirabile
    CNR Institute of Neurosciences, Department of Biomedical Sciences, University of Padova, Viale G Colombo 3, Padova 35121, Italy
    Cardiovasc Res 93:291-301. 2012
    ..The role of the laterality gene Pitx2 in this process is unknown. We aimed to elucidate the molecular events driving left/right patterning in the sinus venosus (SV) myocardium by using a myocardial Pitx2 knockout mouse...
  51. doi Role of connexin40 in the autoregulatory response of the afferent arteriole
    Charlotte Mehlin Sorensen
    Institute of Biomedical Sciences, Division of Renal and Vascular Physiology, University of Copenhagen, Denmark
    Am J Physiol Renal Physiol 303:F855-63. 2012
    ..Connexin40 (Cx40) also plays a significant role in the regulation of renin secretion...
  52. doi Defective Cx40 maintains Cx37 expression but intact Cx40 is crucial for conducted dilations irrespective of hypertension
    Alexander Jobs
    Institut fur Physiologie, Universitat zu Lubeck, Lubeck, Germany
    Hypertension 60:1422-9. 2012
    The gap junction channel protein connexin40 (Cx40) is crucial in vascular and renal physiology, because Cx40-deficient mice exhibit impaired conduction of endothelium-dependent dilations and pronounced hypertension...
  53. pmc Compromised regulation of tissue perfusion and arteriogenesis limit, in an AT1R-independent fashion, recovery of ischemic tissue in Cx40(-/-) mice
    Jennifer S Fang
    Department of Physiology, University of Arizona, Tucson, AZ 85718, USA
    Am J Physiol Heart Circ Physiol 304:H816-27. 2013
    ..hindlimb was reduced, inflammatory response increased, and survival of distal limb tissue compromised in connexin 40 (Cx40)-deficient (Cx40(-/-)) mice...
  54. doi The aldo-keto reductase AKR1B7 coexpresses with renin without influencing renin production and secretion
    Katharina Machura
    Institut fur Physiologie, Universitat Regensburg, D 93053 Regensburg, Germany
    Am J Physiol Renal Physiol 304:F578-84. 2013
    ..In summary, our data suggest that AKR1B7 is not of major relevance for the regulation of renin production and secretion in spite of its striking coregulation with renin expression...
  55. doi Polymorphism in endothelial connexin40 enhances sensitivity to intraluminal pressure and increases arterial stiffness
    Daniel J Chaston
    John Curtin School of Medical Research, The Australian National University, Bldg 131 Garran Rd, Acton Australian Capital Territory 0200 Australia
    Arterioscler Thromb Vasc Biol 33:962-70. 2013
    To determine whether impairment of endothelial connexin40 (Cx40), an effect that can occur in hypertension and aging, contributes to the arterial dysfunction and stiffening in these conditions.
  56. ncbi Gene and pseudogene of the mouse cation-dependent mannose 6-phosphate receptor. Genomic organization, expression, and chromosomal localization
    T Ludwig
    European Molecular Biology Laboratory, Heidelberg, Federal Republic of Germany
    J Biol Chem 267:12211-9. 1992
    ..Therefore, it may represent an additional exon of the functional gene. These two features of the pseudogene suggest that expression of the CD-MPR gene may be regulated by use of different promoters and/or alternative splicing...
  57. ncbi The diversity of connexin genes encoding gap junctional proteins
    K Willecke
    Institut für Genetik Abt Molekulargenetik Universität, Bonn Bundersrepublik Deutschland
    Eur J Cell Biol 56:1-7. 1991
    ..The structural diversity of the connexin genes suggests that they fulfill different functions coordinated with, and perhaps required for, different programs of cellular differentiation...
  58. ncbi Characterization of the mouse loricrin gene: linkage with profilaggrin and the flaky tail and soft coat mutant loci on chromosome 3
    J A Rothnagel
    Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030
    Genomics 23:450-6. 1994
    ..These mouse mutants exhibit a number of changes in their integument, suggesting that abnormalities in these genes may contribute to the mutant phenotype...
  59. ncbi Developmental regulation of connexin 40 gene expression in mouse heart correlates with the differentiation of the conduction system
    B Delorme
    Laboratoire de Genetique et Physiologie du Developpement, Institut de Biologie du Developpement de Marseille, Faculte des Sciences de Luminy, Universite de la Mediterranee, France
    Dev Dyn 204:358-71. 1995
    In adult mouse heart, CX40 is expressed in the atria and the proximal part of the ventricular conduction system (the His bundle and the upper parts of the bundle branches)...
  60. ncbi Multiple members of the connexin gene family participate in preimplantation development of the mouse
    T C Davies
    Department of Zoology, University of Western Ontario, London, Canada
    Dev Genet 18:234-43. 1996
    ..3, Cx31.1, and Cx40 mRNAs accumulate beginning in the eight-cell stage...
  61. pmc Incompatibility of connexin 40 and 43 Hemichannels in gap junctions between mammalian cells is determined by intracellular domains
    S Haubrich
    Abteilung Molekulargenetik, University of Bonn, Germany
    Mol Biol Cell 7:1995-2006. 1996
    Murine connexin 40 (Cx40) and connexin 43 (Cx43) do not form functional heterotypic gap junction channels...
  62. ncbi Heart defects in connexin43-deficient mice
    J Ya
    Department of Anatomy and Embryology, Academic Medical Center, University of Amsterdam, The Netherlands
    Circ Res 82:360-6. 1998
    ....
  63. ncbi Reduced cardiac conduction velocity and predisposition to arrhythmias in connexin40-deficient mice
    S Kirchhoff
    Institut für Genetik Abt Molekulargenetik, Universitat Bonn, Römerstr 164, 53117, Bonn, Germany
    Curr Biol 8:299-302. 1998
    ..In the mouse, connexin40 (Cx40) protein has been detected in endothelial cells of lung and heart and in certain heart muscle cells: atrial ..
  64. pmc Transplacental uptake of glucose is decreased in embryonic lethal connexin26-deficient mice
    H D Gabriel
    Institut fur Genetik, Abt Molekulargenetik, Universitat Bonn, 53117 Bonn, Germany
    J Cell Biol 140:1453-61. 1998
    ....
  65. ncbi Conduction disturbances and increased atrial vulnerability in Connexin40-deficient mice analyzed by transesophageal stimulation
    A Hagendorff
    Department of Cardiology, Institute of Genetics, University of Bonn, Germany
    Circulation 99:1508-15. 1999
    Recently, it has been reported that connexin40 (Cx40) deficiency in targeted mouse mutants is associated with a prolongation of P-wave and QRS complex duration on surface electrograms...
  66. ncbi Cardiac conduction abnormalities in mice lacking the gap junction protein connexin40
    S Verheule
    Department of Medical Physiology and Sports Medicine, Utrecht University, The Netherlands
    J Cardiovasc Electrophysiol 10:1380-9. 1999
    The gap junction protein connexin40 (Cx40) normally is expressed in the murine atrial myocardium and ventricular conduction system. In mice lacking Cx40, several changes in the surface ECG have been described...
  67. ncbi Connexins and impulse propagation in the mouse heart
    J Jalife
    Department of Pharmacology, SUNY Health Science Center, Syracuse, New York 13210, USA
    J Cardiovasc Electrophysiol 10:1649-63. 1999
    ..Three gap junction proteins, known as connexins, are expressed in the heart: Cx40, Cx43, and Cx45...
  68. ncbi Connexin expression in the retina
    G Sohl
    Institut fur Genetik, Abteilung fur Molekulargenetik, Universitat Bonn, Germany
    Brain Res Brain Res Rev 32:138-45. 2000
    ..reactions of the corresponding antibodies, retinae from targeted connexin-deficient mice (Cx31 -/-, Cx32 -/- and Cx40 -/-) were used as negative controls for immunoblot and immunofluorescence analyses of wild-type retina...
  69. ncbi Unique and shared functions of different connexins in mice
    A Plum
    Institut fur Genetik, Universitat Bonn, Roemerstrasse164, D 53117, Bonn, Germany
    Curr Biol 10:1083-91. 2000
    ..To discriminate between the unique and shared functions of Cx43, Cx40 and Cx32, we generated two 'knock-in' mouse lines, Cx43KI32 and Cx43KI40, in which the coding region of the Cx43 ..
  70. ncbi A novel genetic pathway for sudden cardiac death via defects in the transition between ventricular and conduction system cell lineages
    V T Nguyêñ-Trân
    UCSD Salk Program in Molecular Medicine and the UCSD Institute of Molecular Medicine, University of California, San Diego, La Jolla 92093, USA
    Cell 102:671-82. 2000
    ..These studies identify a novel genetic pathway for sudden cardiac death via defects in the transition between ventricular and conduction system cell lineages...
  71. ncbi Epaxial-adaxial-hypaxial regionalisation of the vertebrate somite: evidence for a somitic organiser and a mirror-image duplication
    R Spörle
    Institute of Mammalian Genetics, GSF Research Center for Environment and Health, Ingolstadter Landstrasse 1, 85764 Neuherberg, Germany
    Dev Genes Evol 211:198-217. 2001
    ....
  72. ncbi Functional significance of gap junctional coupling in preimplantation development
    F D Houghton
    Department of Physiology, Dental Sciences Building, The University of Western Ontario, London, Ontario, Canada N6A 5C1
    Biol Reprod 66:1403-12. 2002
    ..New evidence of this diversification is presented using rat blastocyst outgrowths...
  73. pmc Cooperative action of Tbx2 and Nkx2.5 inhibits ANF expression in the atrioventricular canal: implications for cardiac chamber formation
    Petra E M H Habets
    Experimental and Molecular Cardiology Group, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Genes Dev 16:1234-46. 2002
    ..5 on the ANF TBE-NKE, and was able to repress ANF promoter activity. Our data provide a potential mechanism for chamber-restricted gene activity in which the cooperative action of Tbx2 and Nkx2.5 inhibits expression in the AVC...
  74. ncbi Gap junctional connexins in the developing mouse cardiac conduction system
    L Miquerol
    Laboratoire de Génétique at Physiologie du Développement CNRS UMR 6545, Institut de Biologie du Developpement de Marseille, Universite de la Mediterranee, Marseille, France
    Novartis Found Symp 250:80-98; discussion 98-109, 276-9. 2003
    ..the conductive myocytes; Cx45 is weakly expressed in all conductive myocytes, including those of the nodal tissues; Cx40 expression is restricted to the atria and ventricular conduction system...
  75. ncbi Gap junctions in the inner ear: comparison of distribution patterns in different vertebrates and assessement of connexin composition in mammals
    Andrew Forge
    UCL Centre for Auditory Research and Institute of Laryngology and Otology, University College London, London WC1X 8EE, United Kingdom
    J Comp Neurol 467:207-31. 2003
    ..Heteromeric cx26/cx30 connexons may be unique to the inner ear, which could be one factor underlying the non-syndromic character of the deafness caused by mutations in cx26...
  76. ncbi Replacement of connexin40 by connexin45 in the mouse: impact on cardiac electrical conduction
    Sébastien Alcoléa
    Laboratoire de Genetique et Physiologie du Developpement, UMR CNRS 6545, Institut de Biologie du Developpement de Marseille, Universite de la Mediterranee, Marseille, France
    Circ Res 94:100-9. 2004
    ..Cx43, Cx40, and Cx45 are synthesized in the cardiomyocytes, and each of them has a unique cardiac expression pattern...
  77. ncbi Sinoatrial node dysfunction and early unexpected death of mice with a defect of klotho gene expression
    Kyosuke Takeshita
    Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    Circulation 109:1776-82. 2004
    ..Homozygous mutant mice with a defect of klotho gene expression (kl/kl) show multiple age-related disorders and premature death from unknown causes...
  78. ncbi T-box transcription factor Tbx2 represses differentiation and formation of the cardiac chambers
    Vincent M Christoffels
    Experimental and Molecular Cardiology Group, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Dev Dyn 229:763-70. 2004
    ..protein expression in mouse hearts was found to be complementary to that of chamber myocardium-specific genes Nppa, Cx40, Cx43, and Chisel, and was conserved in human...
  79. ncbi An expression atlas of connexin genes in the mouse
    Annalisa Buniello
    Telethon Institute of Genetics and Medicine, Via P Castellino 111, 80131 Naples, Italy
    Genomics 83:812-20. 2004
    ....
  80. pmc Nkx2-5 mutation causes anatomic hypoplasia of the cardiac conduction system
    Patrick Y Jay
    Department of Cardiology, Children s Hospital, Boston, Massachusetts 02115, USA
    J Clin Invest 113:1130-7. 2004
    ..Postnatal conduction defects in Nkx2-5 mutation may result at least in part from a defect in the genetic program that governs the recruitment or retention of embryonic cardiac myocytes in the conduction system...
  81. ncbi Abnormal angiogenesis in Foxo1 (Fkhr)-deficient mice
    Tatsuo Furuyama
    Department of Molecular Genetics and Geriatric Research, National Institute for Longevity Sciences, Kumamoto University, Kumamoto 860 0811, Japan
    J Biol Chem 279:34741-9. 2004
    ..These results suggest that Foxo1 is essential to the ability of endothelial cells to respond properly to a high dose of VEGF, thereby playing a critical role in normal vascular development...
  82. ncbi mRNA expression pattern of multiple members of connexin gene family in normal and abnormal fetal gonads in mouse
    Subhash C Juneja
    Department of Zoology, The University of Western Ontario, London, Canada
    Indian J Physiol Pharmacol 47:147-56. 2003
    ..5 dpc knockout (Cx43-/-) fetuses. The mRNA expression pattern of connexins (Cx26, Cx30.3, Cx31, Cx31.1, Cx32, Cx37, Cx40, Cx43, Cx45, Cx46 and Cx50) was analyzed by RT-PCR...
  83. ncbi The T-Box transcription factor Tbx5 is required for the patterning and maturation of the murine cardiac conduction system
    Ivan P G Moskowitz
    Department of Genetics, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA 02115, USA
    Development 131:4107-16. 2004
    ..Deficiencies in the gap junction protein gene connexin 40 (Cx40), a downstream target of Tbx5, did not account for morphologic conduction system defects in Tbx5(del/+) ..
  84. ncbi The Hand1 and Hand2 transcription factors regulate expansion of the embryonic cardiac ventricles in a gene dosage-dependent manner
    David G McFadden
    Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390 9148, USA
    Development 132:189-201. 2005
    ..These findings demonstrate that Hand factors play pivotal and partially redundant roles in cardiac morphogenesis, cardiomyocyte differentiation and cardiac-specific transcription...
  85. ncbi Discontinuous conduction in mouse bundle branches is caused by bundle-branch architecture
    Toon A B van Veen
    Department of Medical Physiology, University Medical Center Utrecht, Utrecht, The Netherlands
    Circulation 112:2235-44. 2005
    ..The present study was performed to elucidate the mechanism responsible for this slowing of conduction...
  86. ncbi Left and right ventricular contributions to the formation of the interventricular septum in the mouse heart
    Diego Franco
    Department of Experimental Biology, Faculty of Experimental Sciences, University of Jaen, 23071 Jaen, Spain
    Dev Biol 294:366-75. 2006
    ..Examination of the orientation as well as the distribution of labeled cells in clusters provides new insights into the morphogenesis of the septum...
  87. ncbi Endogenous and exogenous NO attenuates conduction of vasoconstrictions along arterioles in the microcirculation
    Barbara Rodenwaldt
    Physiologisches Institut, Universitat Lubeck, Ratzeburger Allee 160, 23538 Lubeck, Germany
    Am J Physiol Heart Circ Physiol 292:H2341-8. 2007
    ..The effects of NO were comparable to those of wild-type animals in Cx40-deficient mice, which excludes Cx40 as a specific target of NO...
  88. ncbi Arrhythmia induced by spatiotemporal overexpression of calreticulin in the heart
    Kiyoko Hattori
    Department of Pediatrics, Graduate School of Medical Science, Kumamoto University, Japan
    Mol Genet Metab 91:285-93. 2007
    ..In addition, the protein level of connexin40 (Cx40), connexin43 (Cx43), components of gap junction, and myocyte-enhancer factor (MEF) 2C, a cardiac-specific ..
  89. ncbi Interplay between cystic fibrosis transmembrane regulator and gap junction channels made of connexins 45, 40, 32 and 50 expressed in oocytes
    Basilio A Kotsias
    Department of Pharmacology and Physiology, University of Rochester School of Medicine, 601 Elmwood Avenue, Rochester, NY 14642 8711, USA
    J Membr Biol 214:1-8. 2006
    ..interaction between CFTR and gap junction channels, we coexpressed in Xenopus oocytes CFTR and either Cx45, Cx40, Cx32 or Cx50 and monitored junctional conductance (G (j)) and its sensitivity to transjunctional voltage (V (j)) ..
  90. ncbi Expression of connexins in embryonic mouse neocortical development
    Cima Cina
    Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada
    J Comp Neurol 504:298-313. 2007
    ..Cx26, Cx36, Cx37, Cx43, and Cx45 were expressed in the developing cortex of mice, Cx30 and Cx32 were absent, while Cx40 was expressed at a very low level...
  91. ncbi Connexin45 cannot replace the function of connexin40 in conducting endothelium-dependent dilations along arterioles
    Stephanie E Wölfle
    Institut fur Physiologie, Universitat zu Lubeck, Germany
    Circ Res 101:1292-9. 2007
    ..Gap junctions in arterioles are composed of different connexins (Cxs) (Cx40, Cx37, Cx45, Cx43), but it is unknown whether Cxs are interchangeable...
  92. pmc Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure
    Jian Fu Chen
    Carolina Cardiovascular Biology Center, Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, NC 27599, USA
    Proc Natl Acad Sci U S A 105:2111-6. 2008
    ..Together, our studies demonstrate essential roles for Dicer in cardiac contraction and indicate that miRNAs play critical roles in normal cardiac function and under pathological conditions...
  93. doi SALL1 truncated protein expression in Townes-Brocks syndrome leads to ectopic expression of downstream genes
    Susan M Kiefer
    Research and Education Service Line, St Louis Veterans Administration Medical Center, U S Department of Veterans Affairs, St Louis, Missouri 63106, USA
    Hum Mutat 29:1133-40. 2008
    ..We propose a model for the pathogenesis of TBS in which truncated Sall1 protein causes derepression of Sall-responsive target genes...
  94. doi Separating genetic and hemodynamic defects in neuropilin 1 knockout embryos
    Elizabeth A V Jones
    Inserm U833, F 75005, Paris, France
    Development 135:2479-88. 2008
    ..and mutants and after culture in no-flow conditions showed down-regulation of the arterial marker genes connexin 40 and ephrin B2 related to the loss of Nrp1 function...
  95. pmc Connexin40 imparts conduction heterogeneity to atrial tissue
    David E Leaf
    Leon H Charney Division of Cardiology, New York University School of Medicine, New York, NY 10016, USA
    Circ Res 103:1001-8. 2008
    ..Connexin40 (Cx40) is an abundant gap junction protein that is expressed in atrial myocytes...
  96. doi In calcineurin-induced cardiac hypertrophy expression of Nav1.5, Cx40 and Cx43 is reduced by different mechanisms
    Marti F A Bierhuizen
    Department of Medical Physiology, Division Heart and Lungs, University Medical Center Utrecht, Yalelaan 50, 3584 CM Utrecht, The Netherlands
    J Mol Cell Cardiol 45:373-84. 2008
    Alterations in expression levels of Na(v)1.5, Cx43 and Cx40 have been frequently reported in cardiac disease and are associated with the development of arrhythmias, but little is known about the underlying molecular mechanisms...
  97. pmc Tbx3 is required for outflow tract development
    Karim Mesbah
    Developmental Biology Institute of Marseilles Luminy, France
    Circ Res 103:743-50. 2008
    ....
  98. pmc Dissection of two Cx37-independent conducted vasodilator mechanisms by deletion of Cx40: electrotonic versus regenerative conduction
    Xavier F Figueroa
    Departamento de Ciencias Fisiologicas, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Chile
    Am J Physiol Heart Circ Physiol 295:H2001-7. 2008
    ..Connexin40 is essential for the ACh-activated regenerative vasodilator mechanism. However, neither connexin40 nor connexin37 is indispensable for the electrotonic spread of hyperpolarizing signals...
  99. doi Formation of the sinus node head and differentiation of sinus node myocardium are independently regulated by Tbx18 and Tbx3
    Cornelia Wiese
    Center for Heart Failure Research, Academic Medical Centre, Meibergdreef 15, 1105AZ Amsterdam, The Netherlands
    Circ Res 104:388-97. 2009
    ..In contrast, Tbx3-deficient embryos formed a morphologically normal SAN, which, however, aberrantly expressed Cx40 and other atrial genes, demonstrating that Tbx3 controls differentiation of SAN head and tail cardiomyocytes but ..
  100. pmc Shox2 is essential for the differentiation of cardiac pacemaker cells by repressing Nkx2-5
    Ramón A Espinoza-Lewis
    Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA
    Dev Biol 327:376-85. 2009
    ..Genetically, the lack of Tbx3 and Hcn4 expression, along with ectopic activation of Nppa, Cx40, and Nkx2-5 in the Shox2(-/-) SAN region, indicates a failure in SAN differentiation...

Research Grants5

  1. Gap Junction Mediated Signaling and Vascular Responses
    Alexander M Simon; Fiscal Year: 2010
    ..In the first specific aim, the role of Cx37 and Cx40 in vascular development and angiogenesis is investigated...
  2. CONTROL OF CONNEXIN TRANSPORT AND ASSEMBLY
    Michael Koval; Fiscal Year: 2004
    ....
  3. INTERCELLULAR COMMUNICATION IN MICROVESSELS
    Brian Duling; Fiscal Year: 2004
    ..Hypothesis 5 - Intercellular communication is mediated by multiple connexins Hypothesis 6- Gap junctional communication plays a role in the establishment of normal vasomotor tone ..
  4. Regulation of the Endothelial Cell Glycocalyx
    Brian Duling; Fiscal Year: 2008
    ..The experiments offer the potential for understanding a new level of microvascular regulation, and for developing strategies to understand the intracellular signaling that leads to modification of the glycocalyx. ..
  5. Molecular determinants of lung barrier function
    Michael Koval; Fiscal Year: 2009
    ....