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The PMP22 Gene and Its Related Diseases

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Abstract

Peripheral myelin protein-22 (PMP22) is primarily expressed in the compact myelin of the peripheral nervous system. Levels of PMP22 have to be tightly regulated since alterations of PMP22 levels by mutations of the PMP22 gene are responsible for >50 % of all patients with inherited peripheral neuropathies, including Charcot–Marie–Tooth type-1A (CMT1A) with trisomy of PMP22, hereditary neuropathy with liability to pressure palsies (HNPP) with heterozygous deletion of PMP22, and CMT1E with point mutations of PMP22. While overexpression and point-mutations of the PMP22 gene may produce gain-of-function phenotypes, deletion of PMP22 results in a loss-of-function phenotype that reveals the normal physiological functions of the PMP22 protein. In this article, we will review the basic genetics, biochemistry and molecular structure of PMP22, followed by discussion of the current understanding of pathogenic mechanisms involving in the inherited neuropathies with mutations in PMP22 gene.

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References

  1. Salzer JL (2003) Polarized domains of myelinated axons. Neuron 40:297–318

    Article  PubMed  CAS  Google Scholar 

  2. Hartline DK, Colman DR (2007) Rapid conduction and the evolution of giant axons and myelinated fibers. Curr Biol 17:R29–R35

    Article  PubMed  CAS  Google Scholar 

  3. Arroyo EJ, Scherer SS (2000) On the molecular architecture of myelinated fibers. Histochem Cell Biol 113:1–18

    Article  PubMed  CAS  Google Scholar 

  4. Scherer SS, Arroyo EJ (2002) Recent progress on the molecular organization of myelinated axons. J Peripher Nerv Syst 7:1–12

    Article  PubMed  CAS  Google Scholar 

  5. Snipes GJ, Suter U, Welcher AA, Shooter EM (1992) Characterization of a novel peripheral nervous system myelin protein (PMP-22/SR13). J Cell Biol 117:225–238

    Article  PubMed  CAS  Google Scholar 

  6. Welcher AA, De LM, Suter U, Snipes GJ, Meakin SO, Shooter EM (1992) Isolation of transcriptionally regulated sequences associated with neuronal and non-neuronal cell interactions. Prog Brain Res 94:163–176

    Article  PubMed  CAS  Google Scholar 

  7. Skre H (1974) Genetic and clinical aspects of Charcot–Marie–Tooth's disease. Clin Genet 6:98–118

    Article  PubMed  CAS  Google Scholar 

  8. Schneider C, King RM, Philipson L (1988) Genes specifically expressed at growth arrest of mammalian cells. Cell 54:787–793

    Article  PubMed  CAS  Google Scholar 

  9. Manfioletti G, Ruaro ME, Del SG, Philipson L, Schneider C (1990) A growth arrest-specific (gas) gene codes for a membrane protein. Mol Cell Biol 10:2924–2930

    PubMed  CAS  Google Scholar 

  10. Kitamura K, Suzuki M, Uyemura K (1976) Purification and partial characterization of two glycoproteins in bovine peripheral nerve myelin membrane. Biochim Biophys Acta 455:806–816

    Article  PubMed  CAS  Google Scholar 

  11. Jetten AM, Suter U (2000) The peripheral myelin protein 22 and epithelial membrane protein family. Prog Nucleic Acid Res Mol Biol 64:97–129

    Article  PubMed  CAS  Google Scholar 

  12. Spreyer P, Kuhn G, Hanemann CO, Gillen C, Schaal H, Kuhn R, Lemke G, Muller HW (1991) Axon-regulated expression of a Schwann cell transcript that is homologous to a 'growth arrest-specific' gene. EMBO J 10:3661–3668

    PubMed  CAS  Google Scholar 

  13. van de Wetering RA, Gabreëls-Festen AA, Kremer H, Kalscheuer VM, Gabreëls FJ, Mariman EC (1999) Regulation and expression of the murine PMP22 gene. Mamm Genome 10:419–22

    Google Scholar 

  14. Suter U, Patel PI (1994) Genetic basis of inherited peripheral neuropathies. Hum Mutat 3:95–102

    Article  PubMed  CAS  Google Scholar 

  15. Chen Y, Medvedev A, Ruzanov P, Marvin KW, Jetten AM (1997) cDNA cloning, genomic structure, and chromosome mapping of the human epithelial membrane protein CL-20 gene (EMP1), a member of the PMP22 family. Genomics 41:40–48

    Article  PubMed  CAS  Google Scholar 

  16. Ohsawa Y, Murakami T, Miyazaki Y, Shirabe T, Sunada Y (2006) Peripheral myelin protein 22 is expressed in human central nervous system. J Neurol Sci 247:11–15

    Article  PubMed  CAS  Google Scholar 

  17. Roux KJ, Amici SA, Notterpek L (2004) The temporospatial expression of peripheral myelin protein 22 at the developing blood–nerve and blood–brain barriers. J Comp Neurol 474:578–588

    Article  PubMed  CAS  Google Scholar 

  18. Parmantier E, Cabon F, Braun C, D'Urso D, Muller HW, Zalc B (1995) Peripheral myelin protein-22 is expressed in rat and mouse brain and spinal cord motoneurons. Eur J Neurosci 7:1080–1088

    Article  PubMed  CAS  Google Scholar 

  19. Taylor V, Welcher AA, Program AE, Suter U (1995) Epithelial membrane protein-1, peripheral myelin protein 22, and lens membrane protein 20 define a novel gene family. J Biol Chem 270:28824–28833

    Article  PubMed  CAS  Google Scholar 

  20. De León M, Nahin RL, Mendoza ME, Ruda MA (1994) SR13/PMP-22 expression in rat nervous system, in PC12 cells, and C6 glial cell lines. J Neurosci Res 38:167–81

  21. Wulf P, Suter U (1999) Embryonic expression of epithelial membrane protein 1 in early neurons. Brain Res Dev Brain Res 116(2):169–80

    Google Scholar 

  22. Parmantier E, Braun C, Thomas JL, Peyron F, Martinez S, Zalc B (1997) PMP-22 expression in the central nervous system of the embryonic mouse defines potential transverse segments and longitudinal columns. J Comp Neurol 378:159–172

    Article  PubMed  CAS  Google Scholar 

  23. Lobsiger CS, Magyar JP, Taylor V, Wulf P, Welcher AA, Program AE, Suter U (1996) Identification and characterization of a cDNA and the structural gene encoding the mouse epithelial membrane protein-1. Genomics 36:379–387

    Article  PubMed  CAS  Google Scholar 

  24. Baechner D, Liehr T, Hameister H, Altenberger H, Grehl H, Suter U, Rautenstrauss B (1995) Widespread expression of the peripheral myelin protein-22 gene (PMP22) in neural and non-neural tissues during murine development. J Neurosci Res 42:733–41

    Google Scholar 

  25. Erne B, Sansano S, Frank M, Schaeren-Wiemers N (2002) Rafts in adult peripheral nerve myelin contain major structural myelin proteins and myelin and lymphocyte protein (MAL) and CD59 as specific markers. J Neurochem 82:550–62

    Google Scholar 

  26. Dickson KM, Bergeron JJ, Shames I, Colby J, Nguyen DT, Chevet E, Thomas DY, Snipes GJ (2002) Association of calnexin with mutant peripheral myelin protein-22 ex vivo: a basis for "gain-of-function" ER diseases. Proc Natl Acad Sci U S A 99:9852–9857

    Article  PubMed  CAS  Google Scholar 

  27. D'Urso D, Müller HW (1997) Ins and outs of peripheral myelin protein-22: mapping transmembrane topology and intracellular sorting. J Neurosci Res 49:551–62

    Google Scholar 

  28. Notterpek L, Roux KJ, Amici SA, Yazdanpour A, Rahner C, Fletcher BS (2001) Peripheral myelin protein 22 is a constituent of intercellular junctions in epithelia. Proc Natl Acad Sci U S A 98:14404–14409

    Article  PubMed  CAS  Google Scholar 

  29. Notterpek L, Shooter EM, Snipes GJ (1997) Upregulation of the endosomal–lysosomal pathway in the trembler-J neuropathy. J Neurosci 17:4190–4200

    PubMed  CAS  Google Scholar 

  30. Haney C, Snipes GJ, Shooter EM, Suter U, Garcia C, Griffin JW, Trapp BD (1996) Ultrastructural distribution of PMP22 in Charcot-Marie-Tooth disease type 1A. J Neuropathol Exp Neurol 55:290–9

    Google Scholar 

  31. Carenini S, Neuberg D, Schachner M, Suter U, Martini R (1999) Localization and functional roles of PMP22 in peripheral nerves of P0-deficient mice. Glia 28:256–64

    Google Scholar 

  32. De LM, Nahin RL, Mendoza ME, Ruda MA (1994) SR13/PMP-22 expression in rat nervous system, in PC12 cells, and C6 glial cell lines. J Neurosci Res 38:167–181

    Article  Google Scholar 

  33. Taylor V, Zgraggen C, Naef R, Suter U (2000) Membrane topology of peripheral myelin protein 22. J Neurosci Res 62:15–27

    Article  PubMed  CAS  Google Scholar 

  34. Pareek S, Suter U, Snipes GJ, Welcher AA, Shooter EM, Murphy RA (1993) Detection and processing of peripheral myelin protein PMP22 in cultured Schwann cells. J Biol Chem 268:10372–10379

    PubMed  CAS  Google Scholar 

  35. D'Urso D, Prior R, Greiner-Petter R, Gabreels-Festen AA, Muller HW (1998) Overloaded endoplasmic reticulum-Golgi compartments, a possible pathomechanism of peripheral neuropathies caused by mutations of the peripheral myelin protein PMP22. J Neurosci 18:731–740

    PubMed  Google Scholar 

  36. Hasse B, Bosse F, Hanenberg H, Muller HW (2004) Peripheral myelin protein 22 kDa and protein zero: domain specific trans-interactions. Mol Cell Neurosci 27:370–378

    Article  PubMed  CAS  Google Scholar 

  37. Sedzik J, Kotake Y, Uyemura K (1998) Purification of PASII/PMP22—an extremely hydrophobic glycoprotein of PNS myelin membrane. Neuroreport 9:1595–1600

    Article  PubMed  CAS  Google Scholar 

  38. Sedzik J, Tsukihara T (2000) Solubilization of PNS myelin membrane proteins by detergents. Neuroreport 11:2559–2563

    Article  PubMed  CAS  Google Scholar 

  39. Sedzik J, Uyemura K, Tsukihara T (2002) Towards crystallization of hydrophobic myelin glycoproteins: P0 and PASII/PMP22. Protein Expr Purif 26:368–377

    Article  PubMed  CAS  Google Scholar 

  40. Mobley CK, Myers JK, Hadziselimovic A, Ellis CD, Sanders CR (2007) Purification and initiation of structural characterization of human peripheral myelin protein 22, an integral membrane protein linked to peripheral neuropathies. Biochemistry 46:11185–11195

    Article  PubMed  CAS  Google Scholar 

  41. Sakakura M, Hadziselimovic A, Wang Z, Schey KL, Sanders CR (2011) Structural basis for the Trembler-J phenotype of Charcot–Marie–Tooth disease. Structure 19:1160–1169

    Article  PubMed  CAS  Google Scholar 

  42. Myers JK, Mobley CK, Sanders CR (2008) The peripheral neuropathy-linked Trembler and Trembler-J mutant forms of peripheral myelin protein 22 are folding-destabilized. Biochemistry 47:10620–10629

    Article  PubMed  CAS  Google Scholar 

  43. Maier M, Berger P, Nave KA, Suter U (2002) Identification of the regulatory region of the peripheral myelin protein 22 (PMP22) gene that directs temporal and spatial expression in development and regeneration of peripheral nerves. Mol Cell Neurosci 20:93–109

    Article  PubMed  CAS  Google Scholar 

  44. Maier M, Castagner F, Berger P, Suter U (2003) Distinct elements of the peripheral myelin protein 22 (PMP22) promoter regulate expression in Schwann cells and sensory neurons. Mol Cell Neurosci 24:803–817

    Article  PubMed  CAS  Google Scholar 

  45. Saberan-Djoneidi D, Sanguedolce V, Assouline Z, Levy N, Passage E, Fontes M (2000) Molecular dissection of the Schwann cell specific promoter of the PMP22 gene. Gene 248:223–231

    Article  PubMed  CAS  Google Scholar 

  46. Hai M, Bidichandani SI, Patel PI (2001) Identification of a positive regulatory element in the myelin-specific promoter of the PMP22 gene. J Neurosci Res 65:508–519

    Article  PubMed  CAS  Google Scholar 

  47. Orfali W, Nicholson RN, Guiot MC, Peterson AC, Snipes GJ (2005) An 8.5-kb segment of the PMP22 promoter responds to loss of axon signals during Wallerian degeneration, but does not respond to specific axonal signals during nerve regeneration. J Neurosci Res 80:37–46

    Article  PubMed  CAS  Google Scholar 

  48. Passage E, Norreel JC, Noack-Fraissignes P, Sanguedolce V, Pizant J, Thirion X, Robaglia-Schlupp A, Pellissier JF, Fontes M (2004) Ascorbic acid treatment corrects the phenotype of a mouse model of Charcot–Marie–Tooth disease. Nat Med 10:396–401

    Article  PubMed  CAS  Google Scholar 

  49. Desarnaud F, Do Thi AN, Brown AM, Lemke G, Suter U, Baulieu EE, Schumacher M (1998) Progesterone stimulates the activity of the promoters of peripheral myelin protein-22 and protein zero genes in Schwann cells. J Neurochem 71:1765–1768

    Article  PubMed  CAS  Google Scholar 

  50. Desarnaud F, Bidichandani S, Patel PI, Baulieu EE, Schumacher M (2000) Glucocorticosteroids stimulate the activity of the promoters of peripheral myelin protein-22 and protein zero genes in Schwann cells. Brain Res 865:12–16

    Article  PubMed  CAS  Google Scholar 

  51. Monk KR, Naylor SG, Glenn TD, Mercurio S, Perlin JR, Dominguez C, Moens CB, Talbot WS (2009) A G protein-coupled receptor is essential for Schwann cells to initiate myelination. Science 325:1402–1405

    Article  PubMed  CAS  Google Scholar 

  52. Monk KR, Oshima K, Jors S, Heller S, Talbot WS (2011) Gpr126 is essential for peripheral nerve development and myelination in mammals. Development 138:2673–2680

    Article  PubMed  CAS  Google Scholar 

  53. Ghislain J, Desmarquet-Trin-Dinh C, Gilardi-Hebenstreit P, Charnay P, Frain M (2003) Neural crest patterning: autoregulatory and crest-specific elements co-operate for Krox20 transcriptional control. Development 130:941–953

    Article  PubMed  CAS  Google Scholar 

  54. Zorick TS, Syroid DE, Brown A, Gridley T, Lemke G (1999) Krox-20 controls SCIP expression, cell cycle exit and susceptibility to apoptosis in developing myelinating Schwann cells. Development 126:1397–1406

    PubMed  CAS  Google Scholar 

  55. Ghislain J, Desmarquet-Trin-Dinh C, Jaegle M, Meijer D, Charnay P, Frain M (2002) Characterisation of cis-acting sequences reveals a biphasic, axon-dependent regulation of Krox20 during Schwann cell development. Development 129:155–166

    PubMed  CAS  Google Scholar 

  56. Reiprich S, Kriesch J, Schreiner S, Wegner M (2010) Activation of Krox20 gene expression by Sox10 in myelinating Schwann cells. J Neurochem 112:744–754

    Article  PubMed  CAS  Google Scholar 

  57. Topilko P, Schneider-Maunoury S, Levi G, Baron-Van Evercooren A, Chennoufi AB, Seitanidou T, Babinet C, Charnay P (1994) Krox-20 controls myelination in the peripheral nervous system. Nature 371:796–799

    Google Scholar 

  58. Bellone E, Di ME, Soriani S, Varese A, Doria LL, Ajmar F, Mandich P (1999) A novel mutation (D305V) in the early growth response 2 gene is associated with severe Charcot–Marie–Tooth type 1 disease. Hum Mutat 14:353–354

    Article  PubMed  CAS  Google Scholar 

  59. Timmerman V, De Jonghe P, Ceuterick C, De Vriendt E, Lofgren A, Nelis E, Warner LE, Lupski JR, Martin JJ, Van Broeckhoven C (1999) Novel missense mutation in the early growth response 2 gene associated with Dejerine–Sottas syndrome phenotype. Neurology 52:1827–1832

    Article  PubMed  CAS  Google Scholar 

  60. Warner LE, Mancias P, Butler IJ, McDonald CM, Keppen L, Koob KG, Lupski JR (1998) Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies. Nat Genet 18:382–384

    Article  PubMed  CAS  Google Scholar 

  61. Warner LE, Svaren J, Milbrandt J, Lupski JR (1999) Functional consequences of mutations in the early growth response 2 gene (EGR2) correlate with severity of human myelinopathies. Hum Mol Genet 8:1245–1251

    Article  PubMed  CAS  Google Scholar 

  62. Nagarajan R, Svaren J, Le N, Araki T, Watson M, Milbrandt J (2001) EGR2 mutations in inherited neuropathies dominant-negatively inhibit myelin gene expression. Neuron 30:355–368

    Article  PubMed  CAS  Google Scholar 

  63. Bondurand N, Girard M, Pingault V, Lemort N, Dubourg O, Goossens M (2001) Human Connexin 32, a gap junction protein altered in the X-linked form of Charcot–Marie–Tooth disease, is directly regulated by the transcription factor SOX10. Hum Mol Genet 10:2783–2795

    Article  PubMed  CAS  Google Scholar 

  64. Jang SW, Srinivasan R, Jones EA, Sun G, Keles S, Krueger C, Chang LW, Nagarajan R, Svaren J (2010) Locus-wide identification of Egr2/Krox20 regulatory targets in myelin genes. J Neurochem 115:1409–1420

    Article  PubMed  CAS  Google Scholar 

  65. LeBlanc SE, Ward RM, Svaren J (2007) Neuropathy-associated Egr2 mutants disrupt cooperative activation of myelin protein zero by Egr2 and Sox10. Mol Cell Biol 27:3521–3529

    Article  PubMed  CAS  Google Scholar 

  66. LeBlanc SE, Jang SW, Ward RM, Wrabetz L, Svaren J (2006) Direct regulation of myelin protein zero expression by the Egr2 transactivator. J Biol Chem 281:5453–5460

    Article  PubMed  CAS  Google Scholar 

  67. Jones EA, Jang SW, Mager GM, Chang LW, Srinivasan R, Gokey NG, Ward RM, Nagarajan R, Svaren J (2007) Interactions of Sox10 and Egr2 in myelin gene regulation. Neuron Glia Biol 3:377–387

    Article  PubMed  Google Scholar 

  68. Jones EA, Brewer MH, Srinivasan R, Krueger C, Sun G, Charney KN, Keles S, Antonellis A, Svaren J (2012) Distal enhancers upstream of the Charcot–Marie–Tooth type 1A disease gene PMP22. Hum Mol Genet 21:1581–1591

    Article  PubMed  CAS  Google Scholar 

  69. Jones EA, Lopez-Anido C, Srinivasan R, Krueger C, Chang LW, Nagarajan R, Svaren J (2011) Regulation of the PMP22 gene through an intronic enhancer. J Neurosci 31:4242–4250

    Article  PubMed  CAS  Google Scholar 

  70. Weterman MA, van Ruissen F, de Wissel M, Bordewijk L, Samijn JP, van der Pol WL, Meggouh F, Baas F (2010) Copy number variation upstream of PMP22 in Charcot–Marie–Tooth disease. Eur J Hum Genet 18:421–428

    Article  PubMed  CAS  Google Scholar 

  71. Zhang F, Seeman P, Liu P, Weterman MA, Gonzaga-Jauregui C, Towne CF, Batish SD, De VE, De JP, Rautenstrauss B, Krause KH, Khajavi M, Posadka J, Vandenberghe A, Palau F, Van ML, Baas F, Timmerman V, Lupski JR (2010) Mechanisms for nonrecurrent genomic rearrangements associated with CMT1A or HNPP: rare CNVs as a cause for missing heritability. Am J Hum Genet 86:892–903

    Article  PubMed  CAS  Google Scholar 

  72. LeBlanc SE, Srinivasan R, Ferri C, Mager GM, Gillian-Daniel AL, Wrabetz L, Svaren J (2005) Regulation of cholesterol/lipid biosynthetic genes by Egr2/Krox20 during peripheral nerve myelination. J Neurochem 93:737–748

    Article  PubMed  CAS  Google Scholar 

  73. Ingram WJ, Wicking CA, Grimmond SM, Forrest AR, Wainwright BJ (2002) Novel genes regulated by Sonic Hedgehog in pluripotent mesenchymal cells. Oncogene 21:8196–8205

    Article  PubMed  CAS  Google Scholar 

  74. Bosse F, Brodbeck J, Muller HW (1999) Post-transcriptional regulation of the peripheral myelin protein gene PMP22/gas3. J Neurosci Res 55:164–177

    Article  PubMed  CAS  Google Scholar 

  75. Bosse F, Zoidl G, Wilms S, Gillen CP, Kuhn HG, Muller HW (1994) Differential expression of two mRNA species indicates a dual function of peripheral myelin protein PMP22 in cell growth and myelination. J Neurosci Res 37:529–537

    Article  PubMed  CAS  Google Scholar 

  76. Ryan MC, Notterpek L, Tobler AR, Liu N, Shooter EM (2000) Role of the peripheral myelin protein 22 N-linked glycan in oligomer stability. J Neurochem 75:1465–1474

    Article  PubMed  CAS  Google Scholar 

  77. Liu N, Yamauchi J, Shooter EM (2004) Recessive, but not dominant, mutations in peripheral myelin protein 22 gene show unique patterns of aggregation and intracellular trafficking. Neurobiol Dis 17:300–309

    Article  PubMed  CAS  Google Scholar 

  78. Tobler AR, Notterpek L, Naef R, Taylor V, Suter U, Shooter EM (1999) Transport of Trembler-J mutant peripheral myelin protein 22 is blocked in the intermediate compartment and affects the transport of the wild-type protein by direct interaction. J Neurosci 19:2027–2036

    PubMed  CAS  Google Scholar 

  79. Shames I, Fraser A, Colby J, Orfali W, Snipes GJ (2003) Phenotypic differences between peripheral myelin protein-22 (PMP22) and myelin protein zero (P0) mutations associated with Charcot–Marie–Tooth-related diseases. J Neuropathol Exp Neurol 62:751–764

    PubMed  CAS  Google Scholar 

  80. Naef R, Adlkofer K, Lescher B, Suter U (1997) Aberrant protein trafficking in Trembler suggests a disease mechanism for hereditary human peripheral neuropathies. Mol Cell Neurosci 9:13–25

    Article  PubMed  CAS  Google Scholar 

  81. Colby J, Nicholson R, Dickson KM, Orfali W, Naef R, Suter U, Snipes GJ (2000) PMP22 carrying the trembler or trembler-J mutation is intracellularly retained in myelinating Schwann cells. Neurobiol Dis 7:561–573

    Article  PubMed  CAS  Google Scholar 

  82. Pareek S, Notterpek L, Snipes GJ, Naef R, Sossin W, Laliberte J, Iacampo S, Suter U, Shooter EM, Murphy RA (1997) Neurons promote the translocation of peripheral myelin protein 22 into myelin. J Neurosci 17:7754–7762

    PubMed  CAS  Google Scholar 

  83. Zoidl G, Blass-Kampmann S, D'Urso D, Schmalenbach C, Müller HW (1995) Retroviral-mediated gene transfer of the peripheral myelin protein PMP22 in Schwann cells: modulation of cell growth. EMBO J 14(6):1122–1128

    PubMed  CAS  Google Scholar 

  84. D'Urso D, Schmalenbach C, Zoidl G, Prior R, Müller HW (1997) Studies on the effects of altered PMP22 expression during myelination in vitro. J Neurosci Res 48(1):31–42

    Article  PubMed  Google Scholar 

  85. Hanemann CO, Rosenbaum C, Kupfer S, Wosch S, Stoegbauer F, Müller HW (1998 Jun) Improved culture methods to expand Schwann cells with altered growth behaviour from CMT1A patients. Glia 23(2):89–98

    Google Scholar 

  86. Nobbio L, Vigo T, Abbruzzese M, Levi G, Brancolini C, Mantero S, Grandis M, Benedetti L, Mancardi G, Schenone A (2004) Impairment of PMP22 transgenic Schwann cells differentiation in culture: implications for Charcot–Marie–Tooth type 1A disease. Neurobiol Dis 16:263–273

    Article  PubMed  CAS  Google Scholar 

  87. Erdem S, Mendell JR, Sahenk Z (1998) Fate of Schwann cells in CMT1A and HNPP: evidence for apoptosis. J Neuropathol Exp Neurol 57(6):635–642

    Article  PubMed  CAS  Google Scholar 

  88. Sancho S, Young P, Suter U (2001) Regulation of Schwann cell proliferation and apoptosis in PMP22-deficient mice and mouse models of Charcot–Marie––Tooth disease type 1A. Brain 124(Pt 11):2177–2187

    Article  PubMed  CAS  Google Scholar 

  89. Hanemann CO, Gabreëls-Festen AA, Stoll G, Müller HW (1997) Schwann cell differentiation in Charcot–Marie–Tooth disease type 1A (CMT1A): normal number of myelinating Schwann cells in young CMT1A patients and neural cell adhesion molecule expression in onion bulbs. Acta Neuropathol 94(4):310–315

    Article  PubMed  CAS  Google Scholar 

  90. Zoidl G, D'Urso D, Blass-Kampmann S, Schmalenbach C, Kuhn R, Müller HW (1997) Influence of elevated expression of rat wild-type PMP22 and its mutant PMP22Trembler on cell growth of NIH3T3 fibroblasts. Cell Tissue Res 287(3):459–470

    Article  PubMed  CAS  Google Scholar 

  91. Amici SA, Dunn WA Jr, Murphy AJ, Adams NC, Gale NW, Valenzuela DM, Yancopoulos GD, Notterpek L (2006) Peripheral myelin protein 22 is in complex with alpha6beta4 integrin, and its absence alters the Schwann cell basal lamina. J Neurosci 26(4):1179–1189

    Article  PubMed  CAS  Google Scholar 

  92. Perkins CS, Aguayo AJ, Bray GM (1981) Schwann cell multiplication in Trembler mice. Neuropathol Appl Neurobiol 7(2):115–126

    Article  PubMed  CAS  Google Scholar 

  93. Robertson AM, Perea J, McGuigan A, King RH, Muddle JR, Gabreels-Festen AA, Thomas PK, Huxley C (2002) Comparison of a new pmp22 transgenic mouse line with other mouse models and human patients with CMT1A. J Anat 200(4):377–390

    Article  PubMed  CAS  Google Scholar 

  94. Fabbretti E, Edomi P, Brancolini C, Schneider C (1995) Apoptotic phenotype induced by overexpression of wild-type gas3/PMP22: its relation to the demyelinating peripheral neuropathy CMT1A. Genes Dev 9(15):1846–1856

    Article  PubMed  CAS  Google Scholar 

  95. Brancolini C, Edomi P, Marzinotto S, Schneider C (2000) Exposure at the cell surface is required for gas3/PMP22 to regulate both cell death and cell spreading: implication for the Charcot–Marie–Tooth type 1A and Dejerine–Sottas diseases. Mol Biol Cell 11(9):2901–2914

    PubMed  CAS  Google Scholar 

  96. Brancolini C, Marzinotto S, Edomi P, Agostoni E, Fiorentini C, Müller HW, Schneider C (1999) Rho-dependent regulation of cell spreading by the tetraspan membrane protein Gas3/PMP22. Mol Biol Cell 10(7):2441–2459

    PubMed  CAS  Google Scholar 

  97. Suh JG, Ichihara N, Saigoh K, Nakabayashi O, Yamanishi T, Tanaka K, Wada K, Kikuchi T (1997) An in-frame deletion in peripheral myelin protein-22 gene causes hypomyelination and cell death of the Schwann cells in the new Trembler mutant mice. Neuroscience 79:735–744

    Article  PubMed  CAS  Google Scholar 

  98. Snipes GJ, Suter U, Shooter EM (1992) Human peripheral myelin protein-22 carries the L2/HNK-1 carbohydrate adhesion epitope. J Neurochem 61(5):1961–1964

    Article  Google Scholar 

  99. Verrier JD, Lau P, Hudson L, Murashov AK, Renne R, Notterpek L (2009) Peripheral myelin protein 22 is regulated post-transcriptionally by miRNA-29a. Glia 57:1265–1279

    Article  PubMed  Google Scholar 

  100. Magyar JP, Martini R, Ruelicke T, Aguzzi A, Adlkofer K, Dembic Z, Zielasek J, Toyka KV, Suter U (1996) Impaired differentiation of Schwann cells in transgenic mice with increased PMP22 gene dosage. J Neurosci 16:5351–5360

    PubMed  CAS  Google Scholar 

  101. Robertson AM, Huxley C, King RH, Thomas PK (1999) Development of early postnatal peripheral nerve abnormalities in Trembler-J and PMP22 transgenic mice. J Anat 195(Pt 3):331–339

    Article  PubMed  Google Scholar 

  102. Niemann S, Sereda MW, Suter U, Griffiths IR, Nave KA (2000) Uncoupling of myelin assembly and schwann cell differentiation by transgenic overexpression of peripheral myelin protein 22. J Neurosci 20:4120–4128

    PubMed  CAS  Google Scholar 

  103. Sahenk Z, Serrano-Munuera C, Chen L, Kakabadze I, Najagara HN (2003) Evidence for impaired axonal regeneration in PMP22 duplication: studies in nerve xenografts. J Peripher Nerv Syst 8:116–127

    Article  PubMed  Google Scholar 

  104. Schuierer MM, Mann CJ, Bildsoe H, Huxley C, Hughes SM (2005) Analyses of the differentiation potential of satellite cells from myoD−/−, mdx, and PMP22 C22 mice. BMC Musculoskelet Disord 6:15

    Article  PubMed  CAS  Google Scholar 

  105. Adlkofer K, Martini R, Aguzzi A, Zielasek J, Toyka KV, Suter U (1995) Hypermyelination and demyelinating peripheral neuropathy in Pmp22-deficient mice. Nat Genet 11:274–280

    Article  PubMed  CAS  Google Scholar 

  106. Attardi LD, Reczek EE, Cosmas C, Demicco EG, McCurrach ME, Lowe SW, Jacks T (2000) PERP, an apoptosis-associated target of p53, is a novel member of the PMP-22/gas3 family. Genes Dev 14:704–718

    PubMed  CAS  Google Scholar 

  107. Ihrie RA, Reczek E, Horner JS, Khachatrian L, Sage J, Jacks T, Attardi LD (2003) Perp is a mediator of p53-dependent apoptosis in diverse cell types. Curr Biol 13:1985–1990

    Article  PubMed  CAS  Google Scholar 

  108. Nowak M, Koster C, Hammerschmidt M (2005) Perp is required for tissue-specific cell survival during zebrafish development. Cell Death Differ 12:52–64

    Article  PubMed  CAS  Google Scholar 

  109. Nestler M, Martin U, Hortschansky P, Saluz HP, Henke A, Munder T (2006) The zinc containing pro-apoptotic protein siva interacts with the peroxisomal membrane protein pmp22. Mol Cell Biochem 287:147–155

    Article  PubMed  CAS  Google Scholar 

  110. Jacobs SB, Basak S, Murray JI, Pathak N, Attardi LD (2007) Siva is an apoptosis-selective p53 target gene important for neuronal cell death. Cell Death Differ 14:1374–1385

    Article  PubMed  CAS  Google Scholar 

  111. Nattkamper H, Halfter H, Khazaei MR, Lohmann T, Gess B, Eisenacher M, Willscher E, Young P (2009) Varying survival of motoneurons and activation of distinct molecular mechanism in response to altered peripheral myelin protein 22 gene dosage. J Neurochem 110:935–946

    Article  PubMed  CAS  Google Scholar 

  112. Roa BB, Dyck PJ, Marks HG, Chance PF, Lupski JR (1993) Dejerine–Sottas syndrome associated with point mutation in the peripheral myelin protein 22 (PMP22) gene. Nat Genet 5:269–273

    Article  PubMed  CAS  Google Scholar 

  113. Abe A, Nakamura K, Kato M, Numakura C, Honma T, Seiwa C, Shirahata E, Itoh A, Kishikawa Y, Hayasaka K (2010) Compound heterozygous PMP22 deletion mutations causing severe Charcot–Marie–Tooth disease type 1. J Hum Genet 55:771–773

    Article  PubMed  Google Scholar 

  114. Al-Thihli K, Rudkin T, Carson N, Poulin C, Melancon S, Der Kaloustian VM (2008) Compound heterozygous deletions of PMP22 causing severe Charcot–Marie–Tooth disease of the Dejerine–Sottas disease phenotype. Am J Med Genet A 146A:2412–2416

    Article  PubMed  Google Scholar 

  115. Saporta MA, Katona I, Zhang X, Roper HP, McClelland L, Macdonald F, Brueton L, Blake J, Suter U, Reilly MM, Shy ME, Li J (2011) Neuropathy in a human without the PMP22 gene. Arch Neurol 68:814–821

    Article  PubMed  Google Scholar 

  116. Amici SA, Dunn WA Jr, Notterpek L (2007) Developmental abnormalities in the nerves of peripheral myelin protein 22-deficient mice. J Neurosci Res 85:238–249

    Article  PubMed  CAS  Google Scholar 

  117. Adlkofer K, Frei R, Neuberg DH, Zielasek J, Toyka KV, Suter U (1997) Heterozygous peripheral myelin protein 22-deficient mice are affected by a progressive demyelinating tomaculous neuropathy. J Neurosci 17:4662–4671

    PubMed  CAS  Google Scholar 

  118. Amici SA, Dunn WA Jr, Murphy AJ, Adams NC, Gale NW, Valenzuela DM, Yancopoulos GD, Notterpek L (2006) Peripheral myelin protein 22 is in complex with alpha6beta4 integrin, and its absence alters the Schwann cell basal lamina. J Neurosci 26:1179–1189

    Article  PubMed  CAS  Google Scholar 

  119. Dyck PJ, Lambert EH (1968) Lower motor and primary sensory neuron diseases with peroneal muscular atrophy: I. Neurologic, genetic, and electrophysiologic findings in hereditary polyneuropathies. Arch Neurol 18:603–618

    Article  PubMed  CAS  Google Scholar 

  120. Li J, Lewis R, Shy M (2003) Charcot–Marie–Tooth disease. In: Aminoff M, Daroff R (eds)Encyclopedia of the Neurological Sciences. Academic Press Waltham, MA, USA, pp. 676–686

  121. Reilly MM, Murphy SM, Laura M (2011) Charcot–Marie–Tooth disease. J Peripher Nerv Syst 16:1–14

    Article  PubMed  Google Scholar 

  122. Patzko A, Shy ME (2011) Update on Charcot–Marie–Tooth disease. Curr Neurol Neurosci Rep 11:78–88

    Article  PubMed  CAS  Google Scholar 

  123. Lupski JR (1992) An inherited DNA rearrangement and gene dosage effect are responsible for the most common autosomal dominant peripheral neuropathy: Charcot–Marie–Tooth disease type 1A. Clin Res 40:645–652

    PubMed  CAS  Google Scholar 

  124. Suter U, Moskow JJ, Welcher AA, Snipes GJ, Kosaras B, Sidman RL, Buchberg AM, Shooter EM (1992) A leucine-to-proline mutation in the putative first transmembrane domain of the 22-kDa peripheral myelin protein in the trembler-J mouse. Proc Natl Acad Sci U S A 89:4382–4386

    Article  PubMed  CAS  Google Scholar 

  125. Raeymaekers P, Timmerman V, Nelis E, Van Hul W, De Jonghe P, Martin JJ, Van Broeckhoven C (1992) Estimation of the size of the chromosome 17p11.2 duplication in Charcot–Marie–Tooth neuropathy type 1a (CMT1a). HMSN Collaborative Research Group. J Med Genet 29:5–11

    Article  PubMed  CAS  Google Scholar 

  126. Sereda M, Griffiths I, Puhlhofer A, Stewart H, Rossner MJ, Zimmerman F, Magyar JP, Schneider A, Hund E, Meinck HM, Suter U, Nave KA (1996) A transgenic rat model of Charcot–Marie–Tooth disease. Neuron 16:1049–1060

    Article  PubMed  CAS  Google Scholar 

  127. Huxley C, Passage E, Robertson AM, Youl B, Huston S, Manson A, Saberan-Djoniedi D, Figarella-Branger D, Pellissier JF, Thomas PK, Fontes M (1998) Correlation between varying levels of PMP22 expression and the degree of demyelination and reduction in nerve conduction velocity in transgenic mice. Hum Mol Genet 7:449–458

    Article  PubMed  CAS  Google Scholar 

  128. Nicholson GA, Valentijn LJ, Cherryson AK, Kennerson ML, Bragg TL, DeKroon RM, Ross DA, Pollard JD, McLeod JG, Bolhuis PA (1994) A frame shift mutation in the PMP22 gene in hereditary neuropathy with liability to pressure palsies. Nat Genet 6:263–266

    Article  PubMed  CAS  Google Scholar 

  129. Li J, Ghandour K, Radovanovic D, Shy RR, Krajewski KM, Shy ME, Nicholson GA (2007) Stoichiometric alteration of PMP22 protein determines the phenotype of HNPP. Arch Neurol 64:974–978

    Article  PubMed  Google Scholar 

  130. Thomas PK, Marques W Jr, Davis MB, Sweeney MG, King RH, Bradley JL, Muddle JR, Tyson J, Malcolm S, Harding AE (1997) The phenotypic manifestations of chromosome 17p11.2 duplication. Brain 120(Pt 3):465–478

    Article  PubMed  Google Scholar 

  131. Krajewski K, Turansky C, Lewis R, Garbern J, Hinderer S, Kamholz J, Shy ME (1999) Correlation between weakness and axonal loss in patients with CMT1A. Ann N Y Acad Sci 883:490–492

    Article  PubMed  CAS  Google Scholar 

  132. Lewis RA, Sumner AJ, Shy ME (2000) Electrophysiological features of inherited demyelinating neuropathies: a reappraisal in the era of molecular diagnosis. Muscle Nerve 23:1472–1487

    Article  PubMed  CAS  Google Scholar 

  133. Lupski JR, Oca-Luna RM, Slaugenhaupt S, Pentao L, Guzzetta V, Trask BJ, Saucedo-Cardenas O, Barker DF, Killian JM, Garcia CA (1991) DNA duplication associated with Charcot–Marie–Tooth disease type 1A. Cell 66:219–232

    Article  PubMed  CAS  Google Scholar 

  134. Krajewski KM, Lewis RA, Fuerst DR, Turansky C, Hinderer SR, Garbern J, Kamholz J, Shy ME (2000) Neurological dysfunction and axonal degeneration in Charcot–Marie–Tooth disease type 1A. Brain 123(Pt 7):1516–1527

    Article  PubMed  Google Scholar 

  135. Gabreels-Festen A, Wetering RV (1999) Human nerve pathology caused by different mutational mechanisms of the PMP22 gene. Ann N Y Acad Sci 883:336–343

    Article  PubMed  CAS  Google Scholar 

  136. Gabreels-Festen AA, Bolhuis PA, Hoogendijk JE, Valentijn LJ, Eshuis EJ, Gabreels FJ (1995) Charcot–Marie–Tooth disease type 1A: morphological phenotype of the 17p duplication versus PMP22 point mutations. Acta Neuropathol 90:645–649

    Article  PubMed  CAS  Google Scholar 

  137. Robertson AM, King RH, Muddle JR, Thomas PK (1997) Abnormal Schwann cell/axon interactions in the Trembler-J mouse. J Anat 190(Pt 3):423–432

    Article  PubMed  Google Scholar 

  138. Timmerman V, Raeymaekers P, De Jonghe P, De Winter G, Swerts L, Jacobs K, Gheuens J, Martin JJ, Vandenberghe A, Van Broeckhoven C (1990) Assignment of the Charcot–Marie–Tooth neuropathy type 1 (CMT 1a) gene to 17p11.2–p12. Am J Hum Genet 47:680–685

    PubMed  CAS  Google Scholar 

  139. Pentao L, Wise CA, Chinault AC, Patel PI, Lupski JR (1992) Charcot–Marie–Tooth type 1A duplication appears to arise from recombination at repeat sequences flanking the 1.5 Mb monomer unit. Nat Genet 2:292–300

    Article  PubMed  CAS  Google Scholar 

  140. Reiter LT, Murakami T, Koeuth T, Pentao L, Muzny DM, Gibbs RA, Lupski JR (1996) A recombination hotspot responsible for two inherited peripheral neuropathies is located near a mariner transposon-like element. Nat Genet 12:288–297

    Article  PubMed  CAS  Google Scholar 

  141. Choi BO, Kim NK, Park SW, Hyun YS, Jeon HJ, Hwang JH, Chung KW (2011) Inheritance of Charcot–Marie–Tooth disease 1A with rare nonrecurrent genomic rearrangement. Neurogenetics 12:51–58

    Article  PubMed  CAS  Google Scholar 

  142. Lewis RA, Sumner AJ (1982) The electrodiagnostic distinctions between chronic familial and acquired demyelinative neuropathies. Neurology 32:592–596

    Article  PubMed  CAS  Google Scholar 

  143. Bostock H, Sears TA, Sherratt RM (1981) The effects of 4-aminopyridine and tetraethylammonium ions on normal and demyelinated mammalian nerve fibres. J Physiol 313:301–315

    PubMed  CAS  Google Scholar 

  144. Bostock H, Sears TA (1976) Continuous conduction in demyelinated mammalian nerve fibers. Nature 263:786–787

    Article  PubMed  CAS  Google Scholar 

  145. Bostock H, Sherratt RM, Sears TA (1978) Overcoming conduction failure in demyelinated nerve fibres by prolonging action potentials. Nature 274:385–387

    Article  PubMed  CAS  Google Scholar 

  146. Rasminsky M, Sears TA (1971) Internodal conduction in normal and demyelinated mammalian single nerve fibres. J Physiol 217:66P–67P

    PubMed  Google Scholar 

  147. Lafontaine S, Rasminsky M, Saida T, Sumner AJ (1982) Conduction block in rat myelinated fibres following acute exposure to anti-galactocerebroside serum. J Physiol 323:287–306

    PubMed  CAS  Google Scholar 

  148. Brill MH, Waxman SG, Moore JW, Joyner RW (1977) Conduction velocity and spike configuration in myelinated fibers: computed dependence on internode distance. J Neurol Neurosurg Psychiatry 40:769–774

    Article  PubMed  CAS  Google Scholar 

  149. Court FA, Sherman DL, Pratt T, Garry EM, Ribchester RR, Cottrell DF, Fleetwood-Walker SM, Brophy PJ (2004) Restricted growth of Schwann cells lacking Cajal bands slows conduction in myelinated nerves. Nature 431:191–195

    Article  PubMed  CAS  Google Scholar 

  150. Saporta MA, Katona I, Lewis RA, Masse S, Shy ME, Li J (2009) Shortened internodal length of dermal myelinated nerve fibres in Charcot–Marie–Tooth disease type 1A. Brain 132:3263–72

    Google Scholar 

  151. Fortun J, Verrier JD, Go JC, Madorsky I, Dunn WA, Notterpek L (2007) The formation of peripheral myelin protein 22 aggregates is hindered by the enhancement of autophagy and expression of cytoplasmic chaperones. Neurobiol Dis 25:252–265

    Article  PubMed  CAS  Google Scholar 

  152. Fortun J, Dunn WA Jr, Joy S, Li J, Notterpek L (2003) Emerging role for autophagy in the removal of aggresomes in Schwann cells. J Neurosci 23:10672–10680

    PubMed  CAS  Google Scholar 

  153. Fortun J, Go JC, Li J, Amici SA, Dunn WA Jr, Notterpek L (2006) Alterations in degradative pathways and protein aggregation in a neuropathy model based on PMP22 overexpression. Neurobiol Dis 22:153–164

    Article  PubMed  CAS  Google Scholar 

  154. Rangaraju S, Verrier JD, Madorsky I, Nicks J, Dunn WA Jr, Notterpek L (2010) Rapamycin activates autophagy and improves myelination in explant cultures from neuropathic mice. J Neurosci 30:11388–11397

    Article  PubMed  CAS  Google Scholar 

  155. Hanemann CO, D'Urso D, Gabreels-Festen AA, Muller HW (2000) Mutation-dependent alteration in cellular distribution of peripheral myelin protein 22 in nerve biopsies from Charcot–Marie–Tooth type 1A. Brain 123(Pt 5):1001–1006

    Article  PubMed  Google Scholar 

  156. Giambonini-Brugnoli G, Buchstaller J, Sommer L, Suter U, Mantei N (2005) Distinct disease mechanisms in peripheral neuropathies due to altered peripheral myelin protein 22 gene dosage or a Pmp22 point mutation. Neurobiol Dis 18:656–668

    Article  PubMed  CAS  Google Scholar 

  157. Vigo T, Nobbio L, Hummelen PV, Abbruzzese M, Mancardi G, Verpoorten N, Verhoeven K, Sereda MW, Nave KA, Timmerman V, Schenone A (2005) Experimental Charcot–Marie–Tooth type 1A: a cDNA microarrays analysis. Mol Cell Neurosci 28:703–714

    Article  PubMed  CAS  Google Scholar 

  158. Nobbio L, Sturla L, Fiorese F, Usai C, Basile G, Moreschi I, Benvenuto F, Zocchi E, De FA, Schenone A, Bruzzone S (2009) P2X7-mediated increased intracellular calcium causes functional derangement in Schwann cells from rats with CMT1A neuropathy. J Biol Chem 284:23146–23158

    Article  PubMed  CAS  Google Scholar 

  159. Saher G, Quintes S, Mobius W, Wehr MC, Kramer-Albers EM, Brugger B, Nave KA (2009) Cholesterol regulates the endoplasmic reticulum exit of the major membrane protein P0 required for peripheral myelin compaction. J Neurosci 29:6094–6104

    Article  PubMed  CAS  Google Scholar 

  160. Berciano MT, Calle E, Fernandez R, Lafarga M (1998) Regulation of Schwann cell numbers in tellurium-induced neuropathy: apoptosis, supernumerary cells and internodal shortening. Acta Neuropathol 95:269–279

    Article  PubMed  CAS  Google Scholar 

  161. Fledrich R, Schlotter-Weigel B, Schnizer TJ, Wichert SP, Stassart RM, zu Horste GM, Klink A, Weiss BG, Haag U, Walter MC, Rautenstrauss B, Paulus W, Rossner MJ, Sereda MW (2012) A rat model of Charcot–Marie–Tooth disease 1A recapitulates disease variability and supplies biomarkers of axonal loss in patients. Brain 135:72–87

    Article  PubMed  Google Scholar 

  162. Kinter J, Lazzati T, Schmid D, Zeis T, Erne B, Lutzelschwab R, Steck AJ, Pareyson D, Peles E, Schaeren-Wiemers N (2012) An essential role of MAG in mediating axon-myelin attachment in Charcot–Marie–Tooth 1A disease. Neurobiol Dis 49C:221–231

    Google Scholar 

  163. Chance PF, Alderson MK, Leppig KA, Lensch MW, Matsunami N, Smith B, Swanson PD, Odelberg SJ, Disteche CM, Bird TD (1993) DNA deletion associated with hereditary neuropathy with liability to pressure palsies. Cell 72:143–151

    Article  PubMed  CAS  Google Scholar 

  164. Shy ME, Scavina MT, Clark A, Krajewski KM, Li J, Kamholz J, Kolodny E, Szigeti K, Fischer RA, Saifi GM, Scherer SS, Lupski JR (2006) T118M PMP22 mutation causes partial loss of function and HNPP-like neuropathy. Ann Neurol 59:358–364

    Article  PubMed  CAS  Google Scholar 

  165. Gonnaud PM, Sturtz F, Fourbil Y, Bonnebouche C, Tranchant C, Warter JM, Chazot G, Bady B, Vial C, Brechard AS (1995) DNA analysis as a tool to confirm the diagnosis of asymptomatic hereditary neuropathy with liability to pressure palsies (HNPP) with further evidence for the occurrence of de novo mutations. Acta Neurol Scand 92:313–318

    Article  PubMed  CAS  Google Scholar 

  166. Mouton P, Tardieu S, Gouider R, Birouk N, Maisonobe T, Dubourg O, Brice A, LeGuern E, Bouche P (1999) Spectrum of clinical and electrophysiologic features in HNPP patients with the 17p11.2 deletion. Neurology 52:1440–1446

    Article  PubMed  CAS  Google Scholar 

  167. Li J, Krajewski K, Lewis RA, Shy ME (2004) Loss-of-function phenotype of hereditary neuropathy with liability to pressure palsies. Muscle Nerve 29:205–210

    Article  PubMed  Google Scholar 

  168. Mandich P, James R, Nassani S, Defferrari R, Bellone E, Mancardi G, Schenone A, Abbruzzese M, Rocchi M, Ajmar F (1995) Molecular diagnosis of hereditary neuropathy with liability to pressure palsies (HNPP) by detection of 17p11.2 deletion in Italian patients. J Neurol 242:295–298

    Article  PubMed  CAS  Google Scholar 

  169. Timmerman V, Lofgren A, Le Guern E, Liang P, De Jonghe P, Martin JJ, Verhalle D, Robberecht W, Gouider R, Brice A, Van Broeckhoven C (1996) Molecular genetic analysis of the 17p11.2 region in patients with hereditary neuropathy with liability to pressure palsies (HNPP). Hum Genet 97:26–34

    Article  PubMed  CAS  Google Scholar 

  170. Li J, Krajewski K, Shy ME, Lewis RA (2002) Hereditary neuropathy with liability to pressure palsy: the electrophysiology fits the name. Neurology 58:1769–1773

    Article  PubMed  Google Scholar 

  171. Horowitz SH, Spollen LE, Yu W (2004) Hereditary neuropathy with liability to pressure palsy: fulminant development with axonal loss during military training. J Neurol Neurosurg Psychiatry 75:1629–1631

    Article  PubMed  CAS  Google Scholar 

  172. Chance PF, Lensch MW, Lipe H, Brown RH Sr, Brown RH Jr, Bird TD (1994) Hereditary neuralgic amyotrophy and hereditary neuropathy with liability to pressure palsies: two distinct genetic disorders. Neurology 44:2253–2257

    Article  PubMed  CAS  Google Scholar 

  173. Amato AA, Gronseth GS, Callerame KJ, Kagan-Hallet KS, Bryan WW, Barohn RJ (1996) Tomaculous neuropathy: a clinical and electrophysiological study in patients with and without 1.5-Mb deletions in chromosome 17p11.2. Muscle Nerve 19:16–22

    Article  PubMed  CAS  Google Scholar 

  174. Earl CJ, Fullerton PM, Wakefield GS, Schutta HS (1964) Hereditary neuropathy, with liability to pressure palsies; a clinical and electrophysiological study of four families. Q J Med 33:481–498

    PubMed  CAS  Google Scholar 

  175. Stogbauer F, Young P, Kuhlenbaumer G, De Jonghe P, Timmerman V (2000) Hereditary recurrent focal neuropathies: clinical and molecular features. Neurology 54:546–551

    Article  PubMed  CAS  Google Scholar 

  176. Andersson PB, Yuen E, Parko K, So YT (2000) Electrodiagnostic features of hereditary neuropathy with liability to pressure palsies. Neurology 54:40–44

    Article  PubMed  CAS  Google Scholar 

  177. Madrid R, Bradley G (1975) The pathology of neuropathies with focal thickening of the myelin sheath (tomaculous neuropathy): studies on the formation of the abnormal myelin sheath. J Neurol Sci 25:415–448

    Article  Google Scholar 

  178. Bai Y, Zhang X, Katona I, Saporta MA, Shy ME, O'Malley HA, Isom LL, Suter U, Li J (2010) Conduction block in PMP22 deficiency. J Neurosci 30:600–608

    Article  PubMed  CAS  Google Scholar 

  179. Sander S, Ouvrier RA, McLeod JG, Nicholson GA, Pollard JD (2000) Clinical syndromes associated with tomacula or myelin swellings in sural nerve biopsies. J Neurol Neurosurg Psychiatry 68:483–488

    Article  PubMed  CAS  Google Scholar 

  180. Cai Z, Sutton-Smith P, Swift J, Cash K, Finnie J, Turnley A, Thompson PD, Blumbergs PC (2002) Tomacula in MAG-deficient mice. J Peripher Nerv Syst 7:181–189

    Article  PubMed  Google Scholar 

  181. Cai Z, Blumbergs PC, Cash K, Rice PJ, Manavis J, Swift J, Ghabriel MN, Thompson PD (2006) Paranodal pathology in Tangier disease with remitting–relapsing multifocal neuropathy. J Clin Neurosci 13:492–497

    Article  PubMed  CAS  Google Scholar 

  182. Cai Z, Finnie JW, Blumbergs PC, Manavis J, Ghabriel MN, Thompson PD (2006) Early paranodal myelin swellings (tomacula) in an avian riboflavin deficiency model of demyelinating neuropathy. Exp Neurol 198:65–71

    Article  PubMed  CAS  Google Scholar 

  183. Bolino A, Bolis A, Previtali SC, Dina G, Bussini S, Dati G, Amadio S, Del Carro U, Mruk DD, Feltri ML, Cheng CY, Quattrini A, Wrabetz L (2004) Disruption of Mtmr2 produces CMT4B1-like neuropathy with myelin outfolding and impaired spermatogenesis. J Cell Biol 167:711–721

    Article  PubMed  CAS  Google Scholar 

  184. Bird TD (1993) Charcot–Marie–Tooth neuropathy type 1 Gene Reviews

  185. Russo M, Laura M, Polke JM, Davis MB, Blake J, Brandner S, Hughes RA, Houlden H, Bennett DL, Lunn MP, Reilly MM (2011) Variable phenotypes are associated with PMP22 missense mutations. Neuromuscul Disord 21:106–114

    Article  PubMed  CAS  Google Scholar 

  186. Gess B, Jeibmann A, Schirmacher A, Kleffner I, Schilling M, Young P (2011) Report of a novel mutation in the PMP22 gene causing an axonal neuropathy. Muscle Nerve 43:605–609

    Article  PubMed  Google Scholar 

  187. Roa BB, Garcia CA, Lupski JR (1991) Charcot–Marie–Tooth disease type 1A: molecular mechanisms of gene dosage and point mutation underlying a common inherited peripheral neuropathy. Int J Neurol 25–26:97–107

    PubMed  Google Scholar 

  188. Patel PI, Roa BB, Welcher AA, Schoener-Scott R, Trask BJ, Pentao L, Snipes GJ, Garcia CA, Francke U, Shooter EM, Lupski JR, Suter U (1992) The gene for the peripheral myelin protein PMP-22 is a candidate for Charcot–Marie–Tooth disease type 1A. Nat Genet 1:159–165

    Article  PubMed  CAS  Google Scholar 

  189. Devaux JJ, Scherer SS (2005) Altered ion channels in an animal model of Charcot–Marie–Tooth disease type IA. J Neurosci 25:1470–1480

    Article  PubMed  CAS  Google Scholar 

  190. Nodera H, Nishimura M, Logigian EL, Herrmann DN, Kaji R (2003) HNPP due to a novel missense mutation of the PMP22 gene. Neurology 60:1863–1864

    Article  PubMed  Google Scholar 

  191. Kovach MJ, Lin JP, Boyadjiev S, Campbell K, Mazzeo L, Herman K, Rimer LA, Frank W, Llewellyn B, Jabs EW, Gelber D, Kimonis VE (1999) A unique point mutation in the PMP22 gene is associated with Charcot–Marie–Tooth disease and deafness. Am J Hum Genet 64:1580–1593

    Article  PubMed  CAS  Google Scholar 

  192. Bort S, Nelis E, Timmerman V, Sevilla T, Cruz-Martinez A, Martinez F, Millan JM, Arpa J, Vilchez JJ, Prieto F, Van Broeckhoven C, Palau F (1997) Mutational analysis of the MPZ, PMP22 and Cx32 genes in patients of Spanish ancestry with Charcot–Marie–Tooth disease and hereditary neuropathy with liability to pressure palsies. Hum Genet 99:746–754

    Article  PubMed  CAS  Google Scholar 

  193. Marques W Jr, Thomas PK, Sweeney MG, Carr L, Wood NW (1998) Dejerine–Sottas neuropathy and PMP22 point mutations: a new base pair substitution and a possible "hot spot" on Ser72. Ann Neurol 43:680–683

    Article  PubMed  CAS  Google Scholar 

  194. Lenssen PP, Gabreels-Festen AA, Valentijn LJ, Jongen PJ, van Beersum SE, van Engelen BG, van Wensen PJ, Bolhuis PA, Gabreels FJ, Mariman EC (1998) Hereditary neuropathy with liability to pressure palsies. Phenotypic differences between patients with the common deletion and a PMP22 frame shift mutation. Brain 121(Pt 8):1451–1458

    Article  PubMed  Google Scholar 

  195. Luigetti M, Conte A, Madia F, Mereu ML, Zollino M, Marangi G, Pomponi MG, Liberatore G, Tonali PA, Sabatelli M (2008) A new single-nucleotide deletion of PMP22 in an HNPP family without recurrent palsies. Muscle Nerve 38:1060–1064

    Article  PubMed  CAS  Google Scholar 

  196. Suter U, Welcher AA, Ozcelik T, Snipes GJ, Kosaras B, Francke U, Billings-Gagliardi S, Sidman RL, Shooter EM (1992) Trembler mouse carries a point mutation in a myelin gene. Nature 356:241–244

    Article  PubMed  CAS  Google Scholar 

  197. Low PA (1976) Hereditary hypertrophic neuropathy in the trembler mouse: Part 1. Histopathological studies: light microscopy. J Neurol Sci 30:327–341

    Article  PubMed  CAS  Google Scholar 

  198. Low PA (1976) Hereditary hypertrophic neuropathy in the trembler mouse: Part 2. Histopathological studies: electron microscopy. J Neurol Sci 30:343–368

    Article  PubMed  CAS  Google Scholar 

  199. Valentijn LJ, Baas F, Wolterman RA, Hoogendijk JE, van den Bosch NH, Zorn I, Gabreels-Festen AW, de Visser M, Bolhuis PA (1992) Identical point mutations of PMP-22 in Trembler-J mouse and Charcot–Marie–Tooth disease type 1A. Nat Genet 2:288–291

    Article  PubMed  CAS  Google Scholar 

  200. Ionasescu VV, Ionasescu R, Searby C, Barker DF (1993) Charcot–Marie–Tooth neuropathy type 1A with both duplication and non-duplication. Hum Mol Genet 2:405–410

    Article  PubMed  CAS  Google Scholar 

  201. Isaacs AM et al (2000) Identification of two new Pmp22 mouse mutants using large-scale mutagenesis and a novel rapid mapping strategy. Hum Mol Genet 9:1865–1871

    Article  PubMed  CAS  Google Scholar 

  202. Ryan MC, Shooter EM, Notterpek L (2002) Aggresome formation in neuropathy models based on peripheral myelin protein 22 mutations. Neurobiol Dis 10:109–118

    Article  PubMed  CAS  Google Scholar 

  203. Madorsky I, Opalach K, Waber A, Verrier JD, Solmo C, Foster T, Dunn WA Jr, Notterpek L (2009) Intermittent fasting alleviates the neuropathic phenotype in a mouse model of Charcot–Marie–Tooth disease. Neurobiol Dis 34:146–154

    Article  PubMed  CAS  Google Scholar 

  204. Rosso G, Negreira C, Sotelo JR, Kun A (2012) Myelinating and demyelinating phenotype of Trembler-J mouse (a model of Charcot–Marie–Tooth human disease) analyzed by atomic force microscopy and confocal microscopy. J Mol Recognit 25:247–255

    Article  PubMed  CAS  Google Scholar 

  205. Kun A, Canclini L, Rosso G, Bresque M, Romeo C, Hanusz A, Cal K, Calliari A, Sotelo SJ, Sotelo JR (2012) F-actin distribution at nodes of Ranvier and Schmidt–Lanterman incisures in mammalian sciatic nerves. Cytoskeleton (Hoboken) 69:486–495

    Article  CAS  Google Scholar 

  206. Fontanini A, Chies R, Snapp EL, Ferrarini M, Fabrizi GM, Brancolini C (2005) Glycan-independent role of calnexin in the intracellular retention of Charcot–Marie–Tooth 1A Gas3/PMP22 mutants. J Biol Chem 280:2378–2387

    Article  PubMed  CAS  Google Scholar 

  207. Naef R, Suter U (1999) Impaired intracellular trafficking is a common disease mechanism of PMP22 point mutations in peripheral neuropathies. Neurobiol Dis 6:1–14

    Article  PubMed  CAS  Google Scholar 

  208. Huxley C, Passage E, Manson A, Putzu G, Figarella-Branger D, Pellissier JF, Fontes M (1996) Construction of a mouse model of Charcot–Marie–Tooth disease type 1A by pronuclear injection of human YAC DNA. Hum Mol Genet 5:563–569

    Article  PubMed  CAS  Google Scholar 

  209. Robaglia-Schlupp A, Pizant J, Norreel JC, Passage E, Saberan-Djoneidi D, Ansaldi JL, Vinay L, Figarella-Branger D, Levy N, Clarac F, Cau P, Pellissier JF, Fontes M (2002) PMP22 overexpression causes dysmyelination in mice. Brain 125:2213–2221

    Article  PubMed  CAS  Google Scholar 

  210. Perea J, Robertson A, Tolmachova T, Muddle J, King RH, Ponsford S, Thomas PK, Huxley C (2001) Induced myelination and demyelination in a conditional mouse model of Charcot-Marie-Tooth disease type 1A. Hum Mol Genet 10:1007–18

    Google Scholar 

  211. Verhamme C, King RH, ten Asbroek AL, Muddle JR, Nourallah M, Wolterman R, Baas F, van Schaik IN (2011) Myelin and axon pathology in a long-term study of PMP22-overexpressing mice. J Neuropathol Exp Neurol 70:386–398

    Article  PubMed  CAS  Google Scholar 

  212. Henry EW, Cowen JS, Sidman RL (1983) Comparison of Trembler and Trembler-J mouse phenotypes: varying severity of peripheral hypomyelination. J Neuropathol Exp Neurol 42:688–706

    Article  PubMed  CAS  Google Scholar 

  213. Kaya F, Belin S, Bourgeois P, Micaleff J, Blin O, Fontes M (2007) Ascorbic acid inhibits PMP22 expression by reducing cAMP levels. Neuromuscul Disord 17:248–253

    Article  PubMed  Google Scholar 

  214. Kaya F, Belin S, Diamantidis G, Fontes M (2008) Ascorbic acid is a regulator of the intracellular cAMP concentration: old molecule, new functions? FEBS Lett 582:3614–3618

    Article  PubMed  CAS  Google Scholar 

  215. Clark MB, Bunge MB (1989) Cultured Schwann cells assemble normal-appearing basal lamina only when they ensheathe axons. Dev Biol 133:393–404

    Article  PubMed  CAS  Google Scholar 

  216. Bunge RP, Bunge MB, Bates M (1989) Movements of the Schwann cell nucleus implicate progression of the inner (axon-related) Schwann cell process during myelination. J Cell Biol 109:273–284

    Article  PubMed  CAS  Google Scholar 

  217. Sereda MW, Meyer zu HG, Suter U, Uzma N, Nave KA (2003) Therapeutic administration of progesterone antagonist in a model of Charcot–Marie–Tooth disease (CMT-1A). Nat Med 9:1533–1537

    Article  PubMed  CAS  Google Scholar 

  218. Pareyson D, Reilly MM, Schenone A, Fabrizi GM, Cavallaro T, Santoro L, Vita G, Quattrone A, Padua L, Gemignani F, Visioli F, Laura M, Radice D, Calabrese D, Hughes RA, Solari A (2011) Ascorbic acid in Charcot–Marie–Tooth disease type 1A (CMT-TRIAAL and CMT-TRAUK): a double-blind randomised trial. Lancet Neurol 10:320–328

    Article  PubMed  CAS  Google Scholar 

  219. Katona I, Wu X, Feely SM, Sottile S, Siskind CE, Miller LJ, Shy ME, Li J (2009) PMP22 expression in dermal nerve myelin from patients with CMT1A. Brain 132:1734–1740

    Article  PubMed  Google Scholar 

  220. Melcangi RC, Magnaghi V, Cavarretta I, Zucchi I, Bovolin P, D'Urso D, Martini L (1999) Progesterone derivatives are able to influence peripheral myelin protein 22 and P0 gene expression: possible mechanisms of action. J Neurosci Res 56:349–357

    Article  PubMed  CAS  Google Scholar 

  221. Horste MG, Nave KA, Sereda MW (2004) PMP22 expression in skin biopsies serves as a marker for disease severity in a model of Charcot–Marie–Tooth disease 1A (CMT1A)

  222. Meyer zu HG, Prukop T, Liebetanz D, Mobius W, Nave KA, Sereda MW (2007) Antiprogesterone therapy uncouples axonal loss from demyelination in a transgenic rat model of CMT1A neuropathy. Ann Neurol 61:61–72

    Article  CAS  Google Scholar 

  223. Egan ME, Pearson M, Weiner SA, Rajendran V, Rubin D, Glockner-Pagel J, Canny S, Du K, Lukacs GL, Caplan MJ (2004) Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects. Science 304:600–602

    Article  PubMed  CAS  Google Scholar 

  224. Khajavi M, Shiga K, Wiszniewski W, He F, Shaw CA, Yan J, Wensel TG, Snipes GJ, Lupski JR (2007) Oral curcumin mitigates the clinical and neuropathologic phenotype of the Trembler-J mouse: a potential therapy for inherited neuropathy. Am J Hum Genet 81:438–453

    Article  PubMed  CAS  Google Scholar 

  225. Saher G, Brugger B, Lappe-Siefke C, Mobius W, Tozawa R, Wehr MC, Wieland F, Ishibashi S, Nave KA (2005) High cholesterol level is essential for myelin membrane growth. Nat Neurosci 8:468–475

    PubMed  CAS  Google Scholar 

  226. Smith KJ, Hall SM (1988) Peripheral demyelination and remyelination initiated by the calcium-selective ionophore ionomycin: in vivo observations. J Neurol Sci 83:37–53

    Article  PubMed  CAS  Google Scholar 

  227. Smith KJ, Kapoor R, Hall SM, Davies M (2001) Electrically active axons degenerate when exposed to nitric oxide. Ann Neurol 49:470–476

    Article  PubMed  CAS  Google Scholar 

  228. Sahenk Z, Chen L, Mendell JR (1999) Effects of PMP22 duplication and deletions on the axonal cytoskeleton. Ann Neurol 45:16–24

    Article  PubMed  CAS  Google Scholar 

  229. Liu N, Varma S, Shooter EM, Tolwani RJ (2005) Enhancement of Schwann cell myelin formation by K252a in the Trembler-J mouse dorsal root ganglion explant culture. J Neurosci Res 79:310–317

    Article  PubMed  CAS  Google Scholar 

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Acknowledgement

This work is, in part, supported by NIH (R01NS066927) and Veterans Affair (BLR&D).

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Authors and Affiliations

  1. VA Tennessee Valley Healthcare System, 1310 24th Avenue South, Nashville, TN, 37212, USA

    Jun Li, Brett Parker, Colin Martyn, Chandramohan Natarajan & Jiasong Guo

  2. Department of Neurology, Vanderbilt Brain Institute, Center for Human Genetics Research, Vanderbilt University School of Medicine, 1161 21st Avenue South, Nashville, TN, 37232, USA

    Jun Li, Brett Parker, Colin Martyn, Chandramohan Natarajan & Jiasong Guo

  3. Department of Neurology, Vanderbilt University, A-0118 Medical Center North, 1161 21st Avenue South, Nashville, TN, 37237, USA

    Jun Li

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Li, J., Parker, B., Martyn, C. et al. The PMP22 Gene and Its Related Diseases. Mol Neurobiol 47, 673–698 (2013). https://doi.org/10.1007/s12035-012-8370-x

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