Inherited demyelinating neuropathies: From gene to disease

Current Opinion in Neurology

Volumn 11, Issue 5, 1998, Pages 545-556

  Martini, Rudolf ^a   Zielasek, Jürgen ^a   Toyka, Klaus V ^a  

^a UNIVERSITY OF WÜRZBURG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CONNEXIN 32; GAP JUNCTION PROTEIN; MYELIN; MYELIN PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; DEMYELINATING NEUROPATHY; DISEASE CLASSIFICATION; GENE; GENE MUTATION; GENETIC DISORDER; HUMAN; INHERITANCE; KNOCKOUT MOUSE; NONHUMAN; PROTEIN EXPRESSION; REVIEW; TRANSGENIC ANIMAL;

ANIMALS; DEMYELINATING DISEASES; DISEASE MODELS, ANIMAL; GENES; HUMANS; MYELIN PROTEINS; MYELIN SHEATH; PERIPHERAL NERVES;

EID: 0031723901     PISSN: 13507540     EISSN: None     Source Type: Journal    
DOI: 10.1097/00019052-199810000-00018     Document Type: Review

References (97)

1. Dyck PJ, Chance P, Lebo R, Carney JA. Hereditary motor and sensory neuropathies In: Peripheral neuropathy. Dyck PJ, Thomas PK, Griffin JW, Low PA, Poduslo JF (editors). Philadelphia: WB Saunders; 1993. pp. 1094-1136.
2. De Jonghe P, Timmerman V, Nelis E, Martin J-J, Van Broeckhoven C. Charcot-Marie-Tooth disease and related peripheral neuropathies. J Periph Nerv Syst 1997; 2:370-387. This is a thorough and well illustrated summary of the known mutations in myelin genes and other gene loci involved in inherited peripheral neuropathies.
3. Ionasescu VV, Searby CC, Ionasescu R, Reisin R, Ruggieri V, Arberas C. Severe Charcot Marie Tooth neuropathy type 1A with 1 base pair deletion and frameshift mutation in the peripheral myelin protein 22 gene. Muscle Nerve 1997; 10:1308-1310.
4. Birouk N, Gouider R, Guern EL, Gugenheim M, Tardieu S, Maisonobe T, et al. Charcot-Marie-Tooth disease type 1A with 17p11 2 duplication. Clinical and electrophysiological phenotype study and factors influencing disease severity in 119 cases. Brain 1997; 120:813-823. Up to date, this is the largest clinical and electrophysiological study on CMT1A patients with proven PMP22 duplication. Although all patients were affected by the PMP22 duplication, there was a significant variability in the onset, progress and severity of the disease, even among members of the same family.
5. Thomas PK, Marques W Jr, Davis MB, Sweeney MG, Bradley JL, Muddle JR, et al. The phenolypic manifestations of chromosome 17p11 2 duplication. Brain 1997; 120:465-478.
6. Young P, Wiebusch H, Stögbauer F, Ringelstein B, Assmann G, Funke H. A novel frameshift mutation in PMP22 accounts for hereditary neuropathy with liability to pressure palsies. Neurology 1997; 48:450-452.
7. Warner LE, Hilz MJ, Appel SH, Killian JM, Kolodny EH, Karpati G, et al. Clinical phenotypes ol different MPZ (P0) mutations may include Charcot-Marie-Tooth 1B, Dejerine-Sottas, and congenital hypomyelination. Neuron 1996; 17:435-449. This is a very important study on the phenotype - genotype correlation in patients with identified mutations of the myelin component P0.
8. Tachi N, Kozuka N, Ohya K, Chiba S, Sasaki K. Tomaculous neuropathy in Charcot-Marie-Tooth disease with myelin protein zero gene mutation. J Neurol Sci 1997; 153:106-109.
9. Ikegami T, Ikeda H, Mitsui T, Hayasaka K, Ishii S. Novel mutation of the myelin P0 gene in a pedigree with Charcot-Marie-Tooth disease. Am J Med Genet 1997; 71:246-248.
10. Komiyama A, Ohnishi A, Izawa K, Yamamori S, Ohashi H, Hasegawa O. De novo mutation Arg98 → Cys of the myelin P0 gene and uncompaction of the major dense line of the myelin sheath in a severe variant of Charcot-Marie-Tooth disease type 1B. J Neurol Sci 1997; 149:103-109.
11. Deschènes SM, Walcott JL, Wexler TL, Scherer SS, Fischbeck KH. Altered trafficking of mutant connexin32. J Neurosci 1997; 17:9077-9084. This very important study shows that mutations with severly impaired Cx32 trafficking or reduced stability of the mutant protein cause particularly severe forms of CMTX, whereas mutations allowing incorporation of Cx32 into the cell membrane are associated with milder forms.
12. Fischbeck KH, Deschènes SM, Bone LJ, Scherer SS. Connexin32 and X-linked Charcot-Marie-Tooth disease. Cold Spring Harb Symp Quant Biol 1996; 61:673-677.
13. Janssen EAM, Kemp S, Hensels GW, Sie OG, Die-Smulders, Hoogendijk JE, et al. Connexin32 gene mutations in X-linked dominant Charcot-Marie-Tooth disease CMTX1. Hum Genet 1997; 99:501-505.
14. Silander K, Meretoja P, Pihko H, Juvonen V, Issakainen J, Aula P, Savontaus ML. Screening for connexin 32 mutations in Charcot-Marie-Tooth disease families with possible X-linked inheritance. Hum Genet 1997; 100:391-397.
15. Ionasescu VV, Searby CC, Ionasescu R, Chatkupt S, Patel N, Koenigsberger R. Dejerine-Sottas neuropathy in mother and son with same point mutation of PMP22 gene. Muscle Nerve 1997; 20:97-99.
16. Suter U, Snipes GJ. Biology and genetics of hereditary motor and sensory neuropathies. Annu Rev Neurosci 1995; 18:45-75.
17. Taylor V, Welcher AA, AMGEN Est Program, Suter U. Epithelial membrane protein-1, peripheral myelin protein 22 and lens membrane protein 20 define a novel gene family. J Biol Chem 1995; 270:28824-28833.
18. Baechner D, Liehr T, Hameister H, Altenberger H, Grehl H, Suter U, Rautenstrauss B. Widespread expression of the peripheral myelin protein-22 gene (pmp22) in neural and non-neural tissues during murine development. J Neurosci Res 1995; 42:733-741.
19. Parmantier E, Cabon F, Braun C, D'Urso D, Müller HW, Zalc B. Peripheral myelin protein-22 is expressed in rat and mouse brain and spinal cord motoneurons. Eur J Neurosci 1995; 7:1080-1088.
20. Parmantier E, Braun C, Thomas JL, Peyron F, Martinez S, Zalc B. PMP-22 expression in the central nervous system of the embryonic mouse defines potential transverse segments and longitudinal columns. J Comp Neurol 1997; 378:159-172.
21. Haney C, Snipes GJ, Shooter EM, Suter U, Garcia C, Griffin JW, Trapp BD. Ultrastructural distribution of PMP22 in Charcot-Marie-Tooth disease type 1A. J Neuropathol Exp Neurol 1996; 55:290-299.
22. Hammer JA, O'Shannessy DJ, De Leon M, Gould R, Zand D, Daune G, Quarles RH. Immunoreactivity of PMP-22, P0, and other 19 to 28kDa glycoproteins in peripheral nerve myelin of mammals and fish with HNK1 and related antibodies. J Neurochem 1993; 35:546-558.
23. Martini R, Schachner M. Molecular bases of myelin formation as revealed by investigations on mice deficient in glial cell surface molecules. Glia 1997; 19:298-310.
24. Adlkofer K, Martini R, Aguzzi A, Zielasek J, Toyka KV, Suter U. Hypermyelination and demyelinating peripheral neuropathy in pmp22-deficient mice. Nature Genet 1995; 11:274-280.
25. Magyar JP, Martini R, Ruelicke T, Aguzzi A, Adlkofer K, Dembic Z, et al. Impaired differentiation of Schwann cells in transgenic mice witn increased PMP22 gene dosage. J Neurosci 1996; 16:5351-5360.
26. Sereda M, Griffiths I, Pühlhofer A, Stewart A, Rossner MJ, Zimmermann F, et al. A transgenic rat model of Charcot-Marie-Tooth disease. Neuron 1996; 16:1049-1060. Rats expressing three extra copies of mouse PMP22 show clinical, electrophysiological and pathological features reminiscent of abnormalities seen in CMT1A patients carrying the PMP duplications. Rats expressing six copies are very severely affected.
27. Zoidl G, Blass-Kampmann S, D'Urso D, Schmalenbach C, Müller HW. Retroviral-mediated gene transfer of the peripheral myelin protein PMP22 in Schwann cells: modulation of cell growth. EMBO J 1995; 14:1122-1128.
28. D'Urso D, Schmalenbach C, Zoidl G, Prior R, Müller HW. Studies on the effects of altered PMP22 expression during myelination in vitro. J Neurosci Res 1997; 48:31-42.
29. Schneider C, King RM, Philipson L. Genes specifically expressed at growth arrest of mammalian cells. Cell 1988; 54:787-792.
30. Lemke G. The molecular genetics of myelination: an update. Glia 1993; 7:263-271.
31. Lee M-J, Brennan A, Blanchard A, Zoidl G, Dong Z, Tabernero A, et al. P0 is constitutively expressed in the rat neural crest and embryonic nerves and is negatively and positively regulated by axons to generate non-myelin forming and myelin forming Schwann cells, respectively. Mol Cell Neurosci 1997; 8:336-350.
32. Martini R, Bollensen E, Schachner M. Immunocytological localization of the major peripheral nervous system glycoprotein P0 and the L2/HNK-1 and L3 carbohydrate structures in developing and adult mouse sciatic nerve. Dev Biol 1988; 129:330-338.
33. Martini R. Expression and functional roles of neural cell surface molecules and extracellular matrix components during development and regeneration of peripheral nerves. J Neurocytol 1994; 23:1-28.
34. Giese KP, Martini R, Lemke G, Soriano P, Schachner M. Disruption of the P0 gene in mice leads to hypomyelination, abnormal expression of recognition molecules, and degeneration of myelin and axons. Cell 1992; 71:565-576.
35. Martini R, Mohajeri MH, Kasper S, Giese KP, Schachner M. Mice doubly deficient in the genes for P0 and myelin basic protein show that both proteins contribute to the formation of the major dense line in peripheral nerve myelin. J Neurosci 1995; 15:4488-4495.
36. Bone LJ, Deschènes SM, Balice-Gordon RJ, Fischbeck KH, Scherer SS. Connexin32 and X-linked Charcot-Marie-Tooth disease. Neurobiol Dis 1997; 4:221-230.
37. Spray DC, Dermietzel R. X-linked dominant Charcot-Marie-Tooth disease and other potential gap-junction diseases of nervous system. Trends Neurosci 1995; 18:256-262.
38. Bergoffen J, Scherer SS, Wang S, Oronzi Scott M, Bone LJ, Paul DL, et al. Connexin mutations in X-linked Charcot-Marie-Tooth disease. Science 1993; 262:2039-2042.
39. Bruzzone R, Ressot C. Connexins, gap junctions and cell-cell signalling in the nervous system. Eur J Neurosci 1997; 9:1-6.
40. Scherer SS. Molecular genetics of demyelination: new wrinkles on an old membrane. Neuron 1997; 18:13-16.
41. Scherer SS, Deschènes SM, Xu YT, Grinspan JB, Fischbeck KH, Paul DL. Connexin32 is a myelin-related protein in the PNS and CNS. J Neurosci 1995; 15:8281-8294.
42. Nelles E, Bützler C, Jung D, Temme A, Gabriel H-D, Dahl U, et al. Defective propagation of signals generated by sympathetic nerve stimulation in the liver of connexin32-deficient mice. Proc Natl Acad Sci USA 1996; 93:9565-9570.
43. Anzini P, Neuberg DH-H, Schachner M, Nelles E, Willecke K, Zielasek J, et al. Structural abnormalities and deficient maintenance of peripheral nerve myelin in mice lacking the gap junction protein connexin32. J Neurosci 1997; 17:4545-4551. Homozygous Cx32-knock-out mice develop normal myelin sheaths for several weeks followed by the development of pathological alterations typically seen in biopsies of CMTX patients.
44. Yoshikawa H, Nishimura T, Nakatuji Y, Fujimura H, Himoro M, Hayasaka K, et al. Elevated expression of messenger RNA for peripheral myelin protein 22 in biopsied peripheral nerves of patients with Charcot-Marie-Tooth disease type 1A. Ann Neurol 1994; 35:445-450.
45. Hanemann CO. Stoll G, D'Urso D, Fricke W, Martin JJ, Van Broeckhoven C, et al. Peripheral myelin protein-22 expression in Charcot-Marie-Tooth disease type 1a sural nerve biopsies. J Neurosci Res 1994; 37:654-659.
46. Nishimura T, Yoshikawa H, Fujimura H, Sakoda S, Yanagihara T. Accumulation of peripheral myelin protein 22 in onion bulbs and Schwann cells of biopsied nerves from patients with Charcot-Marie-Tooth disease type 1A. Acta Neuropathol 1996; 92:454-460.
47. Guénard V, Montag D, Schachner M, Martini R. Onion bulb cells in mice deficient for myelin genes share molecular properties with immature, differentiated non-myelinating, and denervated Schwann cells. Glia 1996; 18:27-38.
48. Hanemann CO, Gabreëls-Festen AAWM, Stoll G, Müller HW. 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 molecules expression in onion bulbs Acta Neuropathol 1997; 94:310-315.
49. Vallat JM, Sindou P, Preux PM, Tabaraud F, Milor AM, Couratier P, et al. Ultrastructural PMP22 expression in inherited demyelinating neuropathies. Ann Neurol 1996; 39:813-817.
50. Gabriel J-M, Erne B, Pareyson D, Sghirlanzoni A, Taroni F, Steck AJ. Gene dosage effects in hereditary peripheral neuropathy. Expression of peripheral myelin protein 22 in Charcot-Marie-Tooth disease type 1A and hereditary neuropathy with liability to pressure palsies nerve biopsies. Neurology 1997; 49:635-1640.
51. Huxley C, Passage E, Manson A, Putzu G, Figarella Branger D, Pellissier JF, Fontes M. Construction of a mouse model of Charcot-Marie-Tooth disease type 1A by pronuclear injection of human YAC DNA. Hum Mol Genet 1996; 5:563-569.
52. Pareek S, Notterpek L, Snipes GJ, Naef R, Sossin W, Laliberté J, et al. Neurons promote translocation of peripheral myelin protein 22 into myelin. J Neurosci 1997; 17:7745-7762.
53. Schenone A, Nobbio L, Caponetto C, Abbruzzese M, Mandich P, Bellone E, et al. Correlation between PMP-22 messenger RNA expression and phenotype in hereditary neuropathy with liability to pressure palsies. Ann Neurol 1997; 42:866-872.
54. Bort S, Nelis E, Timmermann V, Sevilla T, Cruz-Martinez A, Martinez F, et al. 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 1997; 99:746-754.
55. Gabreëls-Festen AAWM, Bolhuis PA, Hoogendijk JE, Valentijn LJ, Eshuis EJHM, Gabreëls FJM. Charcot-Marie-Tooth disease type 1A: morphological phenotype of the 17p duplication versus PMP22 point mutations. Acta Neuropathol 1995; 90:645-649.
56. Tyson J, Ellis D, Fairbrother U, King RH, Muntoni F, Jacobs J, et al. Hereditary demyelinating neuropathy of infancy. A genetically complex syndrome. Brain 1997; 120:47-63.
57. Henry EW, Cowen JS, Sidman RL. Comparison of Trembler and Trembler-J mouse phenotypes: varying severity of peripheral hypomyelination. J Neuropath Exp Neurol 1983; 42:688-706.
58. Notterpek L, Shooter EM, Snipes GJ. Upregulation of the endosomal - lysosomal pathway in the Trembler-J neuropathy. J Neurosci 1997; 17:4190-4200. This paper shows the activation of autophagic pathways in Schwann cells of Tr-J mutants that are indicative of a constant degeneration and turnover of myelin components.
59. D'Urso D, Prior R, Greiner-Petter R, Gabreëls-Festen AAWM, Müller HW. Overloaded endoplasmic reticulum-Golgi compartments, a possible pathomechanism of peripheral neuropathies caused by mutations of the peripheral myelin protein PMP22. J Neurosci 1997; 18:731-740. The authors show that neither Tr nor Tr-J protein is inserted into cell membranes of transfected Schwann cells and HeLa cells, but both are extensively accumulated in the endoplasmic reticulum and Golgi apparatus.
60. ••], but additionally show a dominant negative effect of the mutant protein by interfering with the transport and insertion of the wild-type protein into the plasma membrane.
61. Adlkofer K, Naef R, Suter U. Analysis of compound heterozygous mice reveals that the Trembler mutation can behave as a gain-of-function allele. J Neurosci Res 1997; 49:671-680. By comparing homo- and heterozygous Trmice, homo- and heterozygous PMP22 knock-out mice and double mutants carrying one Tr allele and one knock-out allele, the authors show that the Tr protein can cause a gain-of-function effect.
62. Gabreëls-Festen AAWM, Hoogendijk JE, Meijerink PHS, Gabreëls FJM, Bolhuis PA, van Beersum S. et al. Two divergent types of nerve pathology in patients with different P0 mutations in Charcot-Marie-Tooth disease. Neurology 1996; 47:761-765.
63. Shapiro L, Doyle JP, Hensley P, Colman DR, Hendrickson WA. Crystal structure of the extracellular domain from P0, the major structural protein of peripheral nerve myelin. Neuron 1996; 17:435-449.
64. Thomas FP, Lebo RV, Rosoklija G, Ding X-S, Lovelace RE, Latov N, Hays AP. Tomaculous neuropathy in chromosome 1 Charcot-Marie-Tooth syndrome. Acta Neuropathol 1994; 87:91-97.
65. Tachi N, Kozuka N, Ohya K, Chiba S, Sasaki K. Tomaculous neuropathy in Charcot-Marie-Tooth disease with myelin zero gene mutation. J Neurol Sci 1997; 153:106-109.
66. Bruzzone R, White TW, Scherer SS, Fischbeck KH, Paul D. Null mutations of connexin32 in patients with X-linked Charcot-Marie-Tooth disease. Neuron 1994; 13:1253-1260.
67. Omori Y, Mesnil M, Yamasaki H. Connexin 32 mutations from X-linked Charcot-Mane-Tooth disease patients: functional defects and dominant negative effects. Mol Biol 1996; 7:907-916.
68. Yoshimura T, Satake M, Ohnishi A, Tsutsumi Y, Fujikura J. Mutations of connexin32 in Charcot-Marie-Tooth disease Type X interfere with cell-to cell communication but not cell proliferation and myelin-specific gene expression J Neurosci Res 1998; 51:154-161.
69. Rabadan-Diehl C, Dahl G, Werner R. A connexin-32 mutation associated with Charcot-Marie-Tooth disease does not affect channel formation in oocytes. FEBS Lett 1994; 351:90-94.
70. Oh S, Ri Y, Bennet MVL, Trexler EB, Verselis VK, Bargiello TA. Changes in permeability caused by connexin 32 mutations underlie X-linked Charcot-Marie-Tooth disease. Neuron 1997; 19:927-938. The authors provide evidence, by single channel recording, that N2A cells transfected with distinct Cx32 mutations causing CMTX in humans form channels with significantly reduced pore sizes. In vivo, this reduction might interfere with the rapid exchange of metabolites and second messangers between the periaxonal and abaxonal Schwann cell cytoplasm.
71. Meier C, Moll C. Hereditary neuropathy with liability to pressure palsies. J Neurol 1982; 228:73-95.
72. Jacobs JM, Gregory R. Uncompacted lamellae as a feature of tomaculous neuropathy. Acta Neuropathol 1994; 83:87-91.
73. Windebank AJ. Inherited recurrent focal neuropathies. In: Peripheral neuropathy. 3rd edn. Dyck PJ, Thomas PK, Griffin JW, Low PA, Poduslo JF (editors). Philadelphia: WB Saunders; 1993. pp. 1137-1148.
74. Adlkofer K, Frei R, Neuberg DH-H, Zielasek J, Toyka KV, Suter U. Heterozygous peripheral myelin protein 22-deficient mice are affected by a progressive demyelinating tomaculous neuropathy. J Neurosci 1997; 17:4662-4671. This paper shows that heterozygous PMP22-knock-out mice develop a pathologic phenotype reminiscent of HNPP.
75. Martini R, Zielasek J, Toyka KV, Giese KP, Schachner M. P0-deficient mice show myelin degeneration in peripheral nerves characteristic of inherited human neuropathies. Nature Genet 1995; 11:281-286.
76. •], with an additional presentation of heterozygous females and evidence for random inactivation of the X chromosome carrying the Cx32 gene.
77. Thomas PK, Marques W, Davies MB, Sweeney MG, King RHM, Bradley JL, et al. The phenotypic manifestations of chromosome 17p11.2 duplication. Brain 1997; 120:465-478.
78. Hayasaka K, Himoro M, Sato W, Takada G, Uyemura K, Shimizu N, et al. Charcot-Marie-Tooth neuropathy type 1B is associated with mutations of the myelin P0 gene. Nature Genet 1993; 5:31-34.
79. Kulkens T, Bolhuis PA, Wolterman RA, Kemp S, te Nijenhuis S, Valentijn LJ, et al. Deletion of the serine 34 codon from the major peripheral myelin protein P0 gene in Charcot-Marie-Tooth disease type 1B. Nature Genet 1993; 5:35-39.
80. Hayasaka K, Himoro M, Sawaishi Y, Nanao K, Takahashi T, Takada G, et al. De novo mutation of the myelin P0 gene in Dejerine-Sottas disease (hereditary motor and sensory neuropathy type III). Nature Genet 1993; 5:266-268.
81. Himoro M, Yoshikawa H, Matsui T, Mitsui Y, Takahashi M, Kaido M, et al. New mutation of the myelin P0 gene in a pedigree of Charcot-Marie-Tooth neuropathy type 1. Biochem Mol Biol Int 1993; 31:169-173.
82. Hayasaka K, Takada G, Ionasescu VV. Mutation of the myelin P0 gene in Charcot-Marie-Tooth neuropathy type 1B. Hum Mol Genet 1993; 2:1369-1372.
83. Martini R. Animal models for inherited peripheral neuropathies. J Anat 1997; 191:321-336. An overview comparing the pathological alterations of patients with identified mutations in myelin genes with the phenotypes of rodents with identical or similar mutations.
84. Martini R, Carenini S. Formation and maintenance of the myelin sheath in the peripheral nerve: roles of cell adhesion molecules and the gap junction protein Connexin 32. Microsc Res Tech 1998; 41:403-415.
85. Hahn AF, Brown WF, Koopman WJ, Feasby TE. X-linked dominant hereditary motor and sensory neuropathy. Brain 1990; 113:1511-1525.
86. Tan CC, Ainsworth PJ, Hahn AF, MacLeod PM. Novel mutations in the connexin 32 gene associated with X-linked Charcot-Marie-Tooth disease Hum Mut 1996; 7:167-171.
87. Sander S, Nicholson GA, Ouvrier RA, McLeod JG, Pollard JD. Charcot-Marie-Toolh disease: histopathological features of the peripheral myelin protein (PMP22) duplication (CMT1A) and connexin32 mutations (CMTX1). Muscle Nerve 1998; 21:217-225.
88. Toyka KV, Zielasek J, Ricker K, Adlkofer K, Suter U. Hereditary neuromyotonia: a mouse model associated with deficiency or increased gene dosage of the PMP22 gene. J Neurol Neurosurg Psychiatry 1997; 63:812-813. The first report on the occurrence of neuromyotonia in mice with severe myelin defects.
89. Auger RG. AAEM minimonograph 44: diseases associated with excess motor unit activity. Muscle Nerve 1994; 17:1250-1263.
90. Gow A, Friedrich VL, Lazzarini RA. Many naturally occurring mutations of myelin proteolipid protein impair its intracellular transport. J Neurosci Res 1994; 37:574-583.
91. Gow A, Southwood CM, Lazzarini RA. Disrupted proleolipid trafficking results in oligodendrocyte apoptosis in an animal model of Pelizaeus-Merzbacher disease. J Cell Biol 1998; 140:925-934. Mutant proteolipid protein gene products are shown to accumulate in the cell interior of differentiated oligodendrocytes of jimpy and msd mice, and probably induce apoptosis of these cells.
92. Wong M-H, Filbin MT. Dominant-negative effect on adhesion by myelin P0 protein truncated in its cytoplasmic domain. J Cell Biol 1996; 134:1531-1541.
93. Bird TD, Kraft GH, Lipe HP, Kenney KL, Sumi SM. Clinical and pathological phenotype of the original family with Charcot-Marie-Tooth type 1B: a 20-year study. Ann Neurol 1997; 41:463-469. This extensive study displays a high variability of disability between the members of a large family with an identified P0 point mutation.
94. Shy ME, Arroyo E, Sladky J, Menichelly D, Jiang H, Xu W, et al. Heterozygous P0 knock-out mice develop a peripheral neuropathy that resembles chronic inflammatory demyelinating polyneuropathy. J Neuropathol Exp Neurol 1997; 56:811-821.
95. Schmid CD, Schnell L, Schachner M, Martini R. Peripheral nerves of a mouse model for Charcot-Marie-Tooth Neuropathy 1B show infiltration of macrophages and CD4- and CD8-positive lymphocytes. Soc Neurosci Abstr 1996; 22:835.
96. Hartung H-P, Stoll G, Toyka KV. Immune reactions in the peripheral nervous system. In: Peripheral neuropath; 3rd edn. Dyck PJ, Thomas PK, Griffin JW, Low PA, Poduslo JF (editors). Philadelphia: WB Saunders. 1993. pp. 418-444.
97. Yang X, Skoff RP. Proteolipid protein regulates the survival and differentiation of oligodendrocytes. J Neurosci 1997; 17:2056-2070.