Pathologic and phenotypic alterations in a mouse expressing a connexin47 missense mutation that causes Pelizaeus-Merzbacher-like disease in humans

PLoS Genetics

Volumn 7, Issue 7, 2011, Pages

  Tress, Oliver ^a   Maglione, Marta ^b   Zlomuzica, Armin ^c   May, Dennis ^a   Dicke, Nikolai ^a   Degen, Joachim ^a   Dere, Ekrem ^d   Kettenmann, Helmut ^b   Hartmann, Dieter ^a   Willecke, Klaus ^a  

^a UNIVERSITY OF BONN   (Germany)

^b MAX DELBRÜCK CENTER FOR MOLECULAR MEDICINE   (Germany)

^c RUHR UNIVERSITY BOCHUM   (Germany)

^d SORBONNE UNIVERSITÉ   (France)

Author keywords

[No Author keywords available]

Indexed keywords

BIOCYTIN; CONNEXIN 47; CONNEXIN 32; GAP JUNCTION PROTEIN; ION CHANNEL;

ANIMAL BEHAVIOR; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASTROCYTOSIS; BRAIN DEVELOPMENT; CONTROLLED STUDY; CORPUS CALLOSUM; EMBRYONIC STEM CELL; GAP JUNCTION; GENE; GENE EXPRESSION PROFILING; GENETIC CODE; GJC2 GENE; HUMAN; HUMAN CELL; MISSENSE MUTATION; MOTOR COORDINATION; MOTOR DEVELOPMENT; MOUSE; NEUROPATHOLOGY; NONHUMAN; NYSTAGMUS; OLIGODENDROGLIA; OPEN FIELD BEHAVIOR; PELIZAEUS MERZBACHER DISEASE; PHENOTYPIC VARIATION; ROTAROD TEST; SPASTICITY; ANIMAL; C57BL MOUSE; CELL JUNCTION; GENETICS; METABOLISM; MOUSE MUTANT; MYELIN SHEATH; PATHOLOGY; STEM CELL;

MUS;

ANIMALS; CONNEXINS; CORPUS CALLOSUM; GAP JUNCTIONS; HUMANS; ION CHANNELS; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MUTATION, MISSENSE; MYELIN SHEATH; OLIGODENDROGLIA; PELIZAEUS-MERZBACHER DISEASE; STEM CELLS;

EID: 79960969591     PISSN: 15537390     EISSN: 15537404     Source Type: Journal    
DOI: 10.1371/journal.pgen.1002146     Document Type: Article

References (68)

1. Uhlenberg B, Schuelke M, Rüschendorf F, Ruf N, Kaindl AM, et al. (2004) Mutations in the gene encoding gap junction protein alpha 12 (connexin 46.6) cause Pelizaeus-Merzbacher-like disease. Am J Hum Genet 75: 251-260.
2. Bugiani M, Al Shahwan S, Lamantea E, Bizzi A, Bakhsh E, et al. (2006) GJA12 mutations in children with recessive hypomyelinating leukoencephalopathy. Neurology 67: 273-279.
3. Wolf NI, Cundall M, Rutland P, Rosser E, Surtees R, et al. (2007) Frameshift mutation in GJA12 leading to nystagmus, spastic ataxia and CNS dys-/demyelination. Neurogenetics 8: 39-44.
4. Salviati L, Trevisson E, Baldoin MC, Toldo I, Sartori S, et al. (2007) A novel deletion in the GJA12 gene causes Pelizaeus-Merzbacher-like disease. Neurogenetics 8: 57-60.
5. Henneke M, Combes P, Diekmann S, Bertini E, Brockmann K, et al. (2008) GJA12 mutations are a rare cause of Pelizaeus-Merzbacher-like disease. Neurology 70: 748-754.
6. Wang J, Wang H, Wang Y, Chen T, Wu X, et al. (2010) Two novel gap junction protein alpha 12 gene mutations in two Chinese patients with Pelizaeus-Merzbacher-like disease. Brain Dev 32: 236-243.
7. Henneke M, Gegner S, Hahn A, Plecko-Startinig B, Weschke B, et al. (2010) Clinical neurophysiology in GJA12-related hypomyelination vs Pelizaeus-Merzbacher disease. Neurology 74: 1785-1789.
8. Diekmann S, Henneke M, Burckhardt BC, Gärtner J, (2010) Pelizaeus-Merzbacher-like disease is caused not only by a loss of connexin47 function but also by a hemichannel dysfunction. Eur J Hum Genet 18: 985-992.
9. Orthmann-Murphy JL, Salsano E, Abrams CK, Bizzi A, Uziel G, et al. (2009) Hereditary spastic paraplegia is a novel phenotype for GJA12/GJC2 mutations. Brain 132: 426-438.
10. Ferrell RE, Baty CJ, Kimak MA, Karlsson JM, Lawrence EC, et al. (2010) GJC2 missense mutations cause human lymphedema. Am J Hum Genet 86: 943-948.
11. Orthmann-Murphy JL, Freidin M, Fischer E, Scherer SS, Abrams CK, (2007) Two distinct heterotypic channels mediate gap junction coupling between astrocyte and oligodendrocyte connexins. J Neurosci 27: 13949-13957.
12. Willecke K, Eiberger J, Degen J, Eckardt D, Romualdi A, et al. (2002) Structural and functional diversity of connexin genes in the mouse and human genome. Biol Chem 383: 725-737.
13. Odermatt B, Wellershaus K, Wallraff A, Seifert G, Degen J, et al. (2003) Connexin 47 (Cx47)-deficient mice with enhanced green fluorescent protein reporter gene reveal predominant oligodendrocytic expression of Cx47 and display vacuolized myelin in the CNS. J Neurosci 23: 4549-4559.
14. Nagy JI, Ionescu A, Lynn BD, Rash JE, (2003) Coupling of astrocyte connexins Cx26, Cx30, Cx43 to oligodendrocyte Cx29, Cx32, Cx47: Implications from normal and connexin32 knockout mice. Glia 44: 205-218.
15. Giaume C, Theis M, (2010) Pharmacological and genetic approaches to study connexin-mediated channels in glial cells of the central nervous system. Brain Res Rev 63: 160-176.
16. Ahn M, Lee J, Gustafsson A, Enriquez A, Lancaster E, et al. (2008) Cx29 and Cx32, two connexins expressed by myelinating glia, do not interact and are functionally distinct. J Neurosci Res 86: 992-1006.
17. Nagy JI, Li X, Rempel J, Stelmack G, Patel D, et al. (2001) Connexin26 in adult rodent central nervous system: demonstration at astrocytic gap junctions and colocalization with connexin30 and connexin43. J Comp Neurol 441: 302-323.
18. Theis M, Jauch R, Zhuo L, Speidel D, Wallraff A, et al. (2003) Accelerated hippocampal spreading depression and enhanced locomotory activity in mice with astrocyte-directed inactivation of connexin43. J Neurosci 23: 766-776.
19. Filippov MA, Hormuzdi SG, Fuchs EC, Monyer H, (2003) A reporter allele for investigating connexin 26 gene expression in the mouse brain. Eur J Neurosci 18: 3183-3192.
20. Magnotti LM, Goodenough DA, Paul DL, (2011) Functional heterotypic interactions between astrocyte and oligodendrocyte connexins. Glia 59: 26-34.
21. Altevogt BM, Paul DL, (2004) Four classes of intercellular channels between glial cells in the CNS. J Neurosci 24: 4313-4323.
22. Kamasawa N, Sik A, Morita M, Yasumura T, Davidson KGV, et al. (2005) Connexin-47 and connexin-32 in gap junctions of oligodendrocyte somata, myelin sheaths, paranodal loops and Schmidt-Lanterman incisures: implications for ionic homeostasis and potassium siphoning. Neuroscience 136: 65-86.
23. Maglione M, Tress O, Haas B, Karram K, Trotter J, et al. (2010) Oligodendrocytes in mouse corpus callosum are coupled via gap junction channels formed by connexin47 and connexin32. Glia 58: 1104-1117.
24. Sargiannidou I, Vavlitou N, Aristodemou S, Hadjisavvas A, Kyriacou K, et al. (2009) Connexin32 mutations cause loss of function in Schwann cells and oligodendrocytes leading to PNS and CNS myelination defects. J Neurosci 29: 4736-4749.
25. Orthmann-Murphy JL, Enriquez AD, Abrams CK, Scherer SS, (2007) Loss-of-function GJA12/Connexin47 mutations cause Pelizaeus-Merzbacher-like disease. Mol Cell Neurosci 34: 629-641.
26. Magin TM, McWhir J, Melton DW, (1992) A new mouse embryonic stem cell line with good germ line contribution and gene targeting frequency. Nucleic Acids Res 20: 3795-3796.
27. Rodríguez CI, Buchholz F, Galloway J, Sequerra R, Kasper J, et al. (2000) High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP. Nat Genet 25: 139-140.
28. Kleopa KA, Orthmann JL, Enriquez A, Paul DL, Scherer SS, (2004) Unique distributions of the gap junction proteins connexin29, connexin32, and connexin47 in oligodendrocytes. Glia 47: 346-357.
29. Baumann N, Pham-Dinh D, (2001) Biology of oligodendrocyte and myelin in the mammalian central nervous system. Physiol Rev 81: 871-927.
30. Dobrowolski R, Sasse P, Schrickel JW, Watkins M, Kim J, et al. (2008) The conditional connexin43G138R mouse mutant represents a new model of hereditary oculodentodigital dysplasia in humans. Hum Mol Genet 17: 539-554.
31. Attal J, Théron MC, Houdebine LM, (1999) The optimal use of IRES (internal ribosome entry site) in expression vectors. Genet Anal 15: 161-165.
32. Schütz M, Scimemi P, Majumder P, De Siati RD, Crispino G, et al. (2010) The human deafness-associated connexin 30 T5M mutation causes mild hearing loss and reduces biochemical coupling among cochlear non-sensory cells in knock-in mice. Hum Mol Genet 19: 4759-4773.
33. Meusser B, Hirsch C, Jarosch E, Sommer T, (2005) ERAD: the long road to destruction. Nat Cell Biol 7: 766-772.
34. Parenti R, Cicirata F, Zappalà A, Catania A, La Delia F, et al. (2010) Dynamic expression of Cx47 in mouse brain development and in the cuprizone model of myelin plasticity. Glia 58: 1594-1609.
35. Elias LAB, Wang DD, Kriegstein AR, (2007) Gap junction adhesion is necessary for radial migration in the neocortex. Nature 448: 901-907.
36. Dyer CA, (2002) The structure and function of myelin: from inert membrane to perfusion pump. Neurochem Res 27: 1279-1292.
37. Tetzlaff W, (1982) Tight junction contact events and temporary gap junctions in the sciatic nerve fibres of the chicken during Wallerian degeneration and subsequent regeneration. J Neurocytol 11: 839-858.
38. Wallraff A, Köhling R, Heinemann U, Theis M, Willecke K, et al. (2006) The impact of astrocytic gap junctional coupling on potassium buffering in the hippocampus. J Neurosci 26: 5438-5447.
39. Menichella DM, Majdan M, Awatramani R, Goodenough DA, Sirkowski E, et al. (2006) Genetic and physiological evidence that oligodendrocyte gap junctions contribute to spatial buffering of potassium released during neuronal activity. J Neurosci 26: 10984-10991.
40. Rash JE, (2009) Molecular disruptions of the panglial syncytium block potassium siphoning and axonal saltatory conduction: pertinence to neuromyelitis optica and other demyelinating diseases of the central nervous system. Neuroscience Available at: http://www.ncbi.nlm.nih.gov/pubmed/19850107. Accessed 6 June 2010.
41. Matalon R, Michals K, Sebesta D, Deanching M, Gashkoff P, et al. (1988) Aspartoacylase deficiency and N-acetylaspartic aciduria in patients with Canavan disease. Am J Med Genet 29: 463-471.
42. Matalon R, Michals K, Kaul R, (1995) Canavan disease: from spongy degeneration to molecular analysis. J Pediatr 127: 511-517.
43. Traka M, Wollmann RL, Cerda SR, Dugas J, Barres BA, et al. (2008) Nur7 is a nonsense mutation in the mouse aspartoacylase gene that causes spongy degeneration of the CNS. J Neurosci 28: 11537-11549.
44. Sartori S, Burlina AB, Salviati L, Trevisson E, Toldo I, et al. (2008) Increased level of N-acetylaspartylglutamate (NAAG) in the CSF of a patient with Pelizaeus-Merzbacher-like disease due to mutation in the GJA12 gene. Eur J Paediatr Neurol 12: 348-350.
45. Mochel F, Boildieu N, Barritault J, Sarret C, Eymard-Pierre E, et al. (2010) Elevated CSF N-acetylaspartylglutamate suggests specific molecular diagnostic abnormalities in patients with white matter diseases. Biochim Biophys Acta Available at: http://www.ncbi.nlm.nih.gov/pubmed/20637281. Accessed 29 July 2010.
46. Berger UV, Luthi-Carter R, Passani LA, Elkabes S, Black I, et al. (1999) Glutamate carboxypeptidase II is expressed by astrocytes in the adult rat nervous system. J Comp Neurol 415: 52-64.
47. Zollinger M, Brauchli-Theotokis J, Gutteck-Amsler U, Do KQ, Streit P, et al. (1994) Release of N-acetylaspartylglutamate from slices of rat cerebellum, striatum, and spinal cord, and the effect of climbing fiber deprivation. J Neurochem 63: 1133-1142.
48. Moffett JR, Ross B, Arun P, Madhavarao CN, Namboodiri AMA, (2007) N-Acetylaspartate in the CNS: from neurodiagnostics to neurobiology. Prog Neurobiol 81: 89-131.
49. Li X, Ionescu AV, Lynn BD, Lu S, Kamasawa N, et al. (2004) Connexin47, connexin29 and connexin32 co-expression in oligodendrocytes and Cx47 association with zonula occludens-1 (ZO-1) in mouse brain. Neuroscience 126: 611-630.
50. Li X, Penes M, Odermatt B, Willecke K, Nagy JI, (2008) Ablation of Cx47 in transgenic mice leads to the loss of MUPP1, ZONAB and multiple connexins at oligodendrocyte-astrocyte gap junctions. Eur J Neurosci 28: 1503-1517.
51. Sourisseau T, Georgiadis A, Tsapara A, Ali RR, Pestell R, et al. (2006) Regulation of PCNA and cyclin D1 expression and epithelial morphogenesis by the ZO-1-regulated transcription factor ZONAB/DbpA. Mol Cell Biol 26: 2387-2398.
52. Balda MS, Matter K, (2000) The tight junction protein ZO-1 and an interacting transcription factor regulate ErbB-2 expression. EMBO J 19: 2024-2033.
53. Lima WR, Parreira KS, Devuyst O, Caplanusi A, N'kuli F, et al. (2010) ZONAB promotes proliferation and represses differentiation of proximal tubule epithelial cells. J Am Soc Nephrol 21: 478-488.
54. Ebnet K, Suzuki A, Ohno S, Vestweber D, (2004) Junctional adhesion molecules (JAMs): more molecules with dual functions? J Cell Sci 117: 19-29.
55. Altevogt BM, Kleopa KA, Postma FR, Scherer SS, Paul DL, (2002) Connexin29 is uniquely distributed within myelinating glial cells of the central and peripheral nervous systems. J Neurosci 22: 6458-6470.
56. Menichella DM, Goodenough DA, Sirkowski E, Scherer SS, Paul DL, (2003) Connexins are critical for normal myelination in the CNS. J Neurosci 23: 5963-5973.
57. Klugmann M, Schwab MH, Pühlhofer A, Schneider A, Zimmermann F, et al. (1997) Assembly of CNS myelin in the absence of proteolipid protein. Neuron 18: 59-70.
58. Pernet V, Joly S, Christ F, Dimou L, Schwab ME, (2008) Nogo-A and myelin-associated glycoprotein differently regulate oligodendrocyte maturation and myelin formation. J Neurosci 28: 7435-7444.
59. Collin L, Usiello A, Erbs E, Mathis C, Borrelli E, (2004) Motor training compensates for cerebellar dysfunctions caused by oligodendrocyte ablation. Proc Natl Acad Sci U S A 101: 325-330.
60. Crawford DK, Mangiardi M, Xia X, López-Valdés HE, Tiwari-Woodruff SK, (2009) Functional recovery of callosal axons following demyelination: a critical window. Neuroscience 164: 1407-1421.
61. Eiberger J, Kibschull M, Strenzke N, Schober A, Büssow H, et al. (2006) Expression pattern and functional characterization of connexin29 in transgenic mice. Glia 53: 601-611.
62. Buchholz F, Angrand PO, Stewart AF, (1996) A simple assay to determine the functionality of Cre or FLP recombination targets in genomic manipulation constructs. Nucleic Acids Res 24: 3118-3119.
63. Theis M, Magin TM, Plum A, Willecke K, (2000) General or cell type-specific deletion and replacement of connexin-coding DNA in the mouse. Methods 20: 205-218.
64. Degen J, Meier C, Van Der Giessen RS, Söhl G, Petrasch-Parwez E, et al. (2004) Expression pattern of lacZ reporter gene representing connexin36 in transgenic mice. J Comp Neurol 473: 511-525.
65. Haas S, Brockhaus J, Verkhratsky A, Kettenmann H, (1996) ATP-induced membrane currents in ameboid microglia acutely isolated from mouse brain slices. Neuroscience 75: 257-261.
66. Kressin K, Kuprijanova E, Jabs R, Seifert G, Steinhäuser C, (1995) Developmental regulation of Na+ and K+ conductances in glial cells of mouse hippocampal brain slices. Glia 15: 173-187.
67. Teubner B, Odermatt B, Guldenagel M, Sohl G, Degen J, et al. (2001) Functional expression of the new gap junction gene connexin47 transcribed in mouse brain and spinal cord neurons. J Neurosci 21: 1117-1126.
68. Traub O, Eckert R, Lichtenberg-Fraté H, Elfgang C, Bastide B, et al. (1994) Immunochemical and electrophysiological characterization of murine connexin40 and -43 in mouse tissues and transfected human cells. Eur J Cell Biol 64: 101-112.