Disease mechanisms in inherited neuropathies (original) (raw)

• Lupski, J. R. & Garcia, C. A. in The Metabolic & Molecular Basis of Inherited Disease (eds Scriver, C. R. et al.) 5759–5788 (McGraw-Hill, New York, 2001).
  Google Scholar
• Berger, P., Young, P. & Suter, U. Molecular cell biology of Charcot–Marie–Tooth disease. Neurogenetics 4, 1–15 (2002).
  Article CAS PubMed Google Scholar
• Kleopa, K. A. & Scherer, S. S. Inherited Neuropathies. Neurol. Clin. 20, 679–709 (2002).
  Article PubMed Google Scholar
• Harding, A. E. & Thomas, P. K. The clinical features of hereditary motor and sensory neuropathy types I and II. Brain 103, 259–280 (1980).
  Article CAS PubMed Google Scholar
• Dyck, P. J., Chance, P., Lebo, R. & Carney, J. A. in Peripheral Neuropathy (eds Dyck, P. J. et al.) 1094–1136 (W. B. Saunders, Philadelphia, 1993).
  Google Scholar
• Aguayo, A. J., Attiwell, M., Trecarten, J., Perkins, C. S. & Bray, C. M. Abnormal myelination in transplanted Trembler mouse Schwann cells. Nature 265, 73–75 (1977).
  Article CAS PubMed Google Scholar
• Chance, P. F. et al. DNA deletion associated with hereditary neuropathy with liability to pressure palsies. Cell 72, 143–151 (1993).
  Article CAS PubMed Google Scholar
• Windebank, T. in Peripheral Neuropathy (eds Dyck, P. J. et al.) 1137–1148 (W. B. Saunders, Philadelphia, 1993).
  Google Scholar
• Adlkofer, K. et al. Heterozygous peripheral myelin protein 22-deficient mice are affected by a progressive demyelinating peripheral neuropathy. J. Neurosci. 17, 4662–4671 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Birouk, N. 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 120, 813–823 (1997).
  Article PubMed Google Scholar
• Thomas, P. K. et al. The phenotypic manifestations of chromosome 17p11.2 duplication. Brain 120, 465–478 (1997).
  Article PubMed Google Scholar
• Krajewski, K. M. et al. Neurological dysfunction and axonal degeneration in Charcot–Marie–Tooth disease. Brain 123, 1516–1527 (2000).
  Article PubMed Google Scholar
• Fabrizi, G. M. et al. Clinical and pathological correlations in Charcot–Marie–Tooth neuropathy type 1A with the 17p11.2p12 duplication: a cross-sectional morphometric and immunohistochemical study in twenty cases. Muscle Nerve 21, 869–877 (1998).
  Article CAS PubMed Google Scholar
• Adlkofer, K. et al. Hypermyelination and demyelinating peripheral neuropathy in _Pmp22_-deficient mice. Nature Genet. 11, 274–280 (1995).
  Article CAS PubMed Google Scholar
• Vallat, J. M. et al. Ultrastructural PMP22 expression in inherited demyelinating neuropathies. Ann. Neurol. 39, 813–817 (1996).
  Article CAS PubMed Google Scholar
• Tobler, A. R. et al. 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 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• D'Urso, D., Ehrhardt, P. & Müller, H. W. Peripheral myelin protein 22 and protein zero: a novel association in peripheral nervous system myelin. J. Neurosci. 19, 3396–3403 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Tobler, A. R., Liu, N., Mueller, L. & Shooter, E. M. Differential aggregation of the Trembler and Trembler J mutants of peripheral myelin protein 22. Proc. Natl Acad Sci. USA 99, 483–488 (2002).
  Article CAS PubMed Google Scholar
• Martini, R., Zielasek, J., Toyka, K. V., Giese, K. P. & Schachner, M. Protein zero (P0)-deficient mice show myelin degeneration in peripheral nerves characteristic of inherited human neuropathies. Nature Genet. 11, 281–285 (1995).
  Article CAS PubMed Google Scholar
• Sereda, M. et al. A transgenic rat model of Charcot–Marie–Tooth disease. Neuron 16, 1049–1060 (1996).
  Article CAS PubMed Google Scholar
• Chies, R. et al. Alterations in the Arf6-regulated plasma membrane endosomal recycling pathway in cells overexpressing the tetraspan protein Gas3/PMP22. J. Cell Sci. 116, 987–99 (2003).
  Article CAS PubMed Google Scholar
• Simons, M. et al. Overexpression of the myelin proteolipid protein leads to accumulation of cholesterol and proteolipid protein in endosomes/lysosomes: implications for Pelizaeus–Merzbacher disease. J. Cell Biol. 157, 327–336 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Hasse, B., Bosse, F. & Müller, H. W. Proteins of peripheral myelin are associated with glycosphingolipid/cholesterol-enriched membranes. J. Neurosci. Res. 69, 227–232 (2002).
  Article CAS PubMed Google Scholar
• Erne, B., Sansano, S., Frank, M. & Schaeren-Wiemers, N. 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, 550–562 (2002).
  Article CAS PubMed Google Scholar
• Zoidl, G., Blass-Kampmann, S., D'Urso, D., Schmalenback, C. & Müller, H. W. Retroviral-mediated gene transfer of the peripheral myelin protein PMP22 in Schwann cells: modulation of cell growth. EMBO J. 14, 1122–1128 (1995).
  Article CAS PubMed PubMed Central Google Scholar
• Hanemann, C. O. & Müller, H. W. Pathogenesis of Charcot–Marie–Tooth IA (CMTIA) neuropathy. Trends Neurosci. 21, 282–286 (1998).
  Article CAS PubMed Google Scholar
• Fabbretti, E., Edomi, P., Brancolini, C. & Schneider, C. Apoptotic phenotype induced by overexpression of wild-type gas3/PMP22: its relation to the demyelinating peripheral neuropathy CMT1A. Genes Dev. 9, 1846–1856 (1995).
  Article CAS PubMed Google Scholar
• Brancolini, C. et al. Rho-dependent regulation of cell spreading by the tetraspan membrane protein Gas3/PMP22. Mol. Biol. Cell 10, 2441–2459 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Sancho, S., Young, P. & Suter, U. Regulation of Schwann cell proliferation and apoptosis in PMP22-deficient mice and mouse models of Charcot–Marie–Tooth disease type 1A. Brain 124, 2177–2187 (2001).
  Article CAS PubMed Google Scholar
• Wilson, H. L., Wilson, S. A., Surprenant, A. & North, R. A. Epithelial membrane proteins induce membrane blebbing and interact with the P2X7 receptor C terminus. J. Biol. Chem. 277, 34017–23 (2002).
  Article CAS PubMed Google Scholar
• Stevens, B. & Fields, R. D. Response of Schwann cells to action potentials in development. Science 287, 2267–2271 (2000).
  Article CAS PubMed Google Scholar
• Giese, K. P., Martini, R., Lemke, G., Soriano, P. & Schachner, M. Mouse P0 gene disruption leads to hypomyelination, abnormal expression of recognition molecules, and degeneration of myelin and axons. Cell 71, 565–576 (1992).
  Article CAS PubMed Google Scholar
• Montag, D. et al. Mice deficient for the myelin-associated glycoprotein show subtle abnormalities in myelin. Neuron 13, 229–246 (1994).
  Article CAS PubMed Google Scholar
• Niemann, S., Sereda, M. W., Suter, U., Griffiths, I. R. & Nave, K. A. Uncoupling of myelin assembly and Schwann cell differentiation by transgenic overexpression of peripheral myelin protein 22. J. Neurosci. 20, 4120–4128 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Taylor, V. & Suter, U. Epithelial membrane protein-2 and epithelial membrane protein-3: two novel members of the peripheral myelin protein 22 gene family. Gene 175, 115–120 (1996).
  Article CAS PubMed Google Scholar
• Wadehra, M., Iyer, R., Goodglick, L. & Braun, J. The tetraspan protein epithelial membrane protein-2 interacts with β1 integrins and regulates adhesion. J. Biol. Chem. 277, 41094–100 (2002).
  Article CAS PubMed Google Scholar
• Nave, K. -A. & Boespflug-Tanguy, O. Developmental defects of myelin formation: from X-linked mutations to human dysmyelinating diseases. Neuroscientist 2, 33–43 (1996).
  Article CAS Google Scholar
• Gudz, T. I., Schneider, T. E., Haas, T. A. & Macklin, W. B. Myelin proteolipid protein forms a complex with integrins and may participate in integrin receptor signaling in oligodendrocytes. J. Neurosci. 22, 7398–7407 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Feltri, M. L. et al. Conditional disruption of β1 integrin in Schwann cells impedes interactions with axons. J. Cell Biol. 156, 199–209 (2002). Conditional deletion of β1 integrin in Schwann cells causes a severe neuropathy with missorted axons.
  Article CAS PubMed PubMed Central Google Scholar
• Misko, A., Ferguson, T. & Notterpek, L. Matrix metalloproteinase mediated degradation of basement membrane proteins in Trembler J neuropathy nerves. J. Neurochem. 83, 885–894 (2002).
  Article CAS PubMed Google Scholar
• 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. 49, 671–680 (1997).
  Article CAS PubMed Google Scholar
• Naef, R., Adlkofer, K., Lescher, B. & Suter, U. Aberrant protein trafficking in Trembler suggests a disease mechanism for hereditary human peripheral neuropathies. Mol. Cell. Neurosci. 9, 13–25 (1997).
  Article CAS PubMed Google Scholar
• Naef, R. & Suter, U. Impaired intracellular trafficking is a common disease mechanism of PMP22 point mutations in peripheral neuropathies. Neurobiol. Dis. 6, 1–14 (1999).
  Article CAS PubMed Google Scholar
• D'Urso, D., Schmalenbach, C., Zoidl, G., Prior, R. & Müller, H. W. Studies on the effects of altered PMP22 expression during myelination in vitro. J. Neurosci. Res. 48, 31–42 (1997).
  Article CAS PubMed Google Scholar
• Colby, J. et al. PMP22 carrying the Trembler or Trembler-J mutation is intracellularly retained in myelinating Schwann cells. Neurobiol. Dis. 7, 561–573 (2000).
  Article CAS PubMed Google Scholar
• Dickson, K. M. et al. Association of calnexin with mutant peripheral myelin protein-22 ex vivo: A basis for 'gain-of-function' ER diseases. Proc. Natl Acad. Sci. USA 99, 9852–9857 (2002). PMP22 mutants have a prolonged association with the endoplasmic reticulum chaperone protein calnexin, possibly depleting the pool of calnexin and causing neuropathy.
  Article CAS PubMed PubMed Central Google Scholar
• Isaacs, A. M. et al. Identification of a new Pmp22 mouse mutant and trafficking analysis of a Pmp22 allelic series suggesting that protein aggregates may be protective in _Pmp22_-associated peripheral neuropathy. Mol. Cell. Neurosci. 21, 114–125 (2002).
  Article CAS PubMed Google Scholar
• Pareek, S. et al. Neurons promote the translocation of peripheral myelin protein 22 into myelin. J. Neurosci. 17, 7754–7762 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Southwood, C. M., Garbern, J., Jiang, W. & Gow, A. The unfolded protein response modulates disease severity in Pelizaeus–Merzbacher disease. Neuron 36, 585–596 (2002). Mutants in PLP induce an 'unfolded protein response' in oligodendrocytes; in contrast to most situations, this seems to be adaptive. This finding might be relevant to disease mechanisms in neuropathies.
  Article CAS PubMed PubMed Central Google Scholar
• Denzel, A. et al. Early postnatal death and motor disorders in mice congenitally deficient in calnexin expression. Mol. Cell. Biol. 22, 7398–404 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Notterpek, L., Shooter, E. M. & Snipes, G. J. Upregulation of the endosomal-lysosomal pathway in the Trembler-J neuropathy. J. Neurosci. 17, 4190–4200 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Notterpek, L., Ryan, M. C., Tobler, A. R. & Shooter, E. M. PMP22 accumulation in aggresomes: implications for CMT1A pathology. Neurobiol. Dis. 6, 450–460 (1999).
  Article CAS PubMed Google Scholar
• Ryan, M. C., Shooter, E. M. & Notterpek, L. Aggresome formation in neuropathy models based on peripheral myelin protein 22 mutations. Neurobiol. Dis. 10, 109–118 (2002).
  Article CAS PubMed Google Scholar
• Gamp, A. C. et al. LIMP-2/LGP85 deficiency causes ureteric pelvic junction obstruction, deafness and peripheral neuropathy in mice. Hum. Mol. Genet. 12, 631–46 (2003).
  Article CAS PubMed Google Scholar
• Lemke, G. & Axel, R. Isolation and sequence of a cDNA encoding the major structural protein of peripheral myelin. Cell 40, 501–508 (1985).
  Article CAS PubMed Google Scholar
• Shapiro, L., Doyle, J. P., Hensley, P., Colman, D. R. & Hendrickson, W. A. Crystal stucture of the extracellular domain from P0, the major structural protein of peripheral nerve myelin. Neuron 17, 435–449 (1996).
  Article CAS PubMed Google Scholar
• Martini, R., Mohajeri, M. H., Kasper, S., Giese, K. P. & 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. 15, 4488–4495 (1995).
  Article CAS PubMed PubMed Central Google Scholar
• D'Urso, D. et al. Protein zero of peripheral nerve myelin: biosynthesis, membrane insertion, and evidence for homotypic interaction. Neuron 4, 449–460 (1990).
  Article CAS PubMed Google Scholar
• Filbin, M. T., Walsh, F. S., Trapp, B. D., Pizzey, J. A. & Tennekoon, G. I. Role of P0 protein as a homophilic adhesion molecule. Nature 344, 871–872 (1990).
  Article CAS PubMed Google Scholar
• Xu, W. B. et al. Mutations in the cytoplasmic domain of P0 reveal a role for PKC-mediated phosphorylation in adhesion and myelination. J. Cell Biol. 155, 439–445 (2001). A CMT1B mutation that abolishes the protein kinase C phosphorylation of P0 causes loss of P0-mediated adhesion, providing an important clue towards signal transduction mediated by P0.
  Article CAS PubMed PubMed Central Google Scholar
• Wrabetz, L. et al. P0 glycoprotein overexpression causes congenital hypomyelination of peripheral nerves. J. Cell Biol. 148, 1021–1033 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Yin, X. et al. Schwann cell myelination requires timely and precise targeting of P0 protein. J. Cell Biol. 148, 1009–1020 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Previtali, S. C. et al. Epitope-tagged P0 glycoprotein causes Charcot—Marie–Tooth-like neuropathy in transgenic mice. J. Cell Biol. 151, 1035–1045 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Willecke, K. et al. Structural and functional diversity of connexin genes in the mouse and human genome. Biol. Chem. 383, 725–737 (2002).
  Article CAS PubMed Google Scholar
• White, T. W. & Paul, D. L. Genetic diseases and gene knockouts reveal diverse connexin functions. Annu. Rev. Physiol. 61, 283–310 (1999).
  Article CAS PubMed Google Scholar
• Bergoffen, J. et al. Connexin mutations in X-linked Charcot–Marie–Tooth disease. Science 262, 2039–2042 (1993).
  Article CAS PubMed Google Scholar
• Anzini, P. et al. Structural abnormalities and deficient maintenance of peripheral nerve myelin in mice lacking the gap junction protein connexin32. J. Neurosci. 17, 4545–4561 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Scherer, S. S. et al. Connexin32-null mice develop a demyelinating peripheral neuropathy. Glia 24, 8–20 (1998).
  Article CAS PubMed Google Scholar
• Balice-Gordon, R. J., Bone, L. J. & Scherer, S. S. Functional gap junctions in the Schwann cell myelin sheath. J. Cell Biol. 142, 1095–1104 (1998). Dye transfer studies demonstrate that incisures contain 'reflexive' gap junctions that provide a radial pathway for diffusion of small molecules across the myelin sheath. The correct functioning of this system might be crucial for maintaining myelin sheaths.
  Article CAS PubMed PubMed Central Google Scholar
• Altevogt, B. M., Kleopa, K. A., Postma, F. R., Scherer, S. S. & Paul, D. L. Cx29 is uniquely distributed within myelinating glial cells of the central and peripheral nervous systems. J. Neurosci. 22, 6458–6470 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Li, X. et al. Connexin29 expression, immunocytochemistry and freeze-fracture replica immunogold labelling (FRIL) in sciatic nerve. Eur. J. Neurosci. 16, 795–806 (2002).
  Article PubMed PubMed Central Google Scholar
• Lewis, R. A., Sumner, A. J. & Shy, M. E. Electrophysiological features of inherited demyelinating neuropathies: a reappraisal in the era of molecular diagnosis. Muscle Nerve 23, 1472–1487 (2000).
  Article CAS PubMed Google Scholar
• Hahn, A., Ainsworth, P. J., Bolton, C. F., Bilbao, J. M. & Vallat, J. -M. Pathological findings in the X-linked form of Charcot–Marie–Tooth disease: a morphometric and ultrastructural analysis. Acta Neuropathol. 101, 129–139 (2001).
  CAS PubMed Google Scholar
• Odermatt, B. et al. 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 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Menichella, D. M., Goodenough, D. A., Sirkowski, E., Scherer, S. S. & Paul, D. L. Connexins are critical for normal myelination in the central nervous system. J. Neurosci. 23, 5963–5973 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Kleopa, K. A., Yum, S. W. & Scherer, S. S. Cellular mechanisms of connexin32 mutations associated with CNS manifestations. J. Neurosci. Res. 68, 522–534 (2002).
  Article CAS PubMed Google Scholar
• Yum, S. W., Kleopa, K. A., Shumas, S. & Scherer, S. S. Diverse trafficking abnormalities for connexin32 mutants causing CMTX. Neurobiol. Dis. 11, 43–52 (2002).
  Article CAS PubMed Google Scholar
• Bruzzone, R., T. W. White, S. S. Scherer, Fischbeck, K. H. & Paul, D. L. Null mutations of connexin32 in patients with X-linked Charcot–Marie–Tooth disease. Neuron 13, 1253–1260 (1994).
  Article CAS PubMed Google Scholar
• Rouan, F. et al. Trans-dominant inhibition of connexin-43 by mutant connexin-26: implications for dominant connexin disorders affecting epidermal differentiation. J. Cell Sci. 114, 2105–2113 (2001).
  CAS PubMed Google Scholar
• VanSlyke, J. K., Deschênes, S. M. & Musil, L. S. Intracellular transport, assembly, and degradation of wild-type and disease-linked mutant gap junction proteins. Mol. Biol. Cell 11, 1933–1946 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Abrams, C. K., Oh, S., Ri, Y. & Bargiello, T. A. Mutations in connexin 32: the molecular and biophysical bases for the X-linked form of Charcot–Marie–Tooth disease. Brain Res. Rev. 32, 203–214 (2000).
  Article CAS PubMed Google Scholar
• Castro, C., Gomez-Hernandez, J. M., Silander, K. & Barrio, L. C. Altered formation of hemichannels and gap junction channels caused by C-terminal connexin-32 mutations. J. Neurosci. 19, 3752–3760 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Tang, X., Fenton, M. J. & Amar, S. Identification and functional characterization of a novel binding site on TNF-α promoter. Proc. Natl Acad. Sci. USA 100, 4096–4101 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Moriwaki, Y. et al. Mycobacterium bovis bacillus Calmette-Guerin and its cell wall complex induce a novel lysosomal membrane protein, SIMPLE, that bridges the missing link between lipopolysaccharide and p53-inducible gene, LITAF (PIG7) and estrogen-inducible gene, EET-1. J. Biol. Chem. 276, 23065–23076 (2001).
  Article CAS PubMed Google Scholar
• Liu, H., Nakagawa, T., Kanematsu, T., Uchida, T. & Tsuji, S. Isolation of 10 differentially expressed cDNAs in differentiated Neuro2a cells induced through controlled expression of the GD3 synthase gene. J. Neurochem. 72, 1781–1790 (1999).
  Article CAS PubMed Google Scholar
• Cuesta, A. et al. The gene encoding ganglioside-induced differentiation-associated protein 1 is mutated in axonal Charcot–Marie–Tooth type 4A disease. Nature Genet. 30, 22–25 (2002).
  Article CAS PubMed Google Scholar
• Baxter, R. V. et al. Ganglioside-induced differentiation-associated protein-1 is mutant in Charcot–Marie–Tooth disease type 4A/8q21. Nature Genet. 30, 21–22 (2002).
  Article CAS PubMed Google Scholar
• Berger, P., Bonneick, S., Willi, S., Wymann, M. & Suter, U. Loss of phosphatase activity in myotubularin-related protein 2 is associated with Charcot–Marie–Tooth disease type 4B1. Hum. Mol. Genet. 11, 1569–1579 (2002).
  Article CAS PubMed Google Scholar
• Bolino, A. et al. Molecular characterization and expression analysis of Mtmr2, a mouse homologue of MTMR2, the myotubularin-related-2 gene mutated in CMT4B. Gene 283, 17–26 (2002).
  Article CAS PubMed Google Scholar
• Laporte, J., Blondeau, F., Buj-Bello, A. & Mandel, J. L. The myotubularin family: from genetic disease to phosphoinositide metabolism. Trends Genet. 17, 221–228 (2001).
  Article CAS PubMed Google Scholar
• Wishart, M. J. & Dixon, J. E. PTEN and myotubularin phosphatases: from 3-phosphoinositide dephosphorylation to disease. Phosphatase and tensin homolog deleted on chromosome ten. Trends Cell Biol. 12, 579–585 (2002).
  Article CAS PubMed Google Scholar
• Schaletzky, J. et al. Phosphatidylinositol-5-phosphate activation and conserved substrate specificity of the myotubularin phosphatidylinositol 3-phosphatases. Curr. Biol. 13, 504–509 (2003).
  Article CAS PubMed Google Scholar
• Kim, S. A., Vacratsis, P. O., Firestein, R., Cleary, M. L. & Dixon, J. E. Regulation of myotubularin-related (MTMR) 2 phosphatidylinositol phosphatase by MTMR5, a catalytically inactive phosphatase. Proc. Natl Acad. Sci. USA 100, 4492–4497 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Nandukar, H. H. et al. Identification of myotubularin as the lipid phosphatase catalytic subunit associated with the 3-phosphatase adapter protein, 3-PAP. Proc. Natl Acad. Sci. USA 100, 8660–8665 (2003).
  Article CAS Google Scholar
• Kalaydjieva, L. et al. N-myc downstream-regulated gene 1 is mutated in hereditary motor and sensory neuropathy-Lom. Am. J. Hum. Genet. 67, 47–58 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Gillespie, C. S. et al. Peripheral demyelination and neuropathic pain behavior in periaxin-deficient mice. Neuron 26, 523–531 (2000). Prx −/− mice develop a demyelinating neuropathy with enhanced sensitivity to pain; these findings mirror those in PRX -null patients.
  Article CAS PubMed Google Scholar
• Gillespie, C. S., Sherman, D. L., Blair, G. E. & Brophy, P. J. Periaxin, a novel protein of myelinating Schwann cells with a possible role in axonal ensheathment. Neuron 12, 497–508 (1994).
  Article CAS PubMed Google Scholar
• Scherer, S. S., Xu, Y. -T., Bannerman, P., Sherman, D. L. & Brophy, P. J. Periaxin expression in myelinating Schwann cells: modulation by axon-glial interactions and polarized localization during development. Development 121, 4265–4273 (1995).
  CAS PubMed Google Scholar
• Sherman, D. L., Fabrizi, C., Gillespie, C. S. & Brophy, P. J. Specific disruption of a Schwann cell dystrophin-related protein complex in a demyelinating neuropathy. Neuron 30, 677–687 (2001).
  Article CAS PubMed Google Scholar
• Rambukkana, A., Zanazzi, G., Tapinos, N. & Salzer, J. L. Contact-dependent demyelination by Mycobacterium leprae in the absence of immune cells. Science 296, 927–931 (2002).
  Article CAS PubMed Google Scholar
• Topilko, P. et al. Krox-20 controls myelination in the peripheral nervous system. Nature 371, 796–799 (1994).
  Article CAS PubMed Google Scholar
• Warner, L. E. et al. Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies. Nature Genet. 18, 382–384 (1998).
  Article CAS PubMed Google Scholar
• Nagarajan, R. et al. EGR2 mutations in inherited neuropathies dominant-negatively inhibit myelin gene expression. Neuron 30, 355–368 (2001). EGR2 mutants that cause demyelinating neuropathies reduce the expression of myelin-related genes by wild-type EGR2 in a dominant manner.
  Article CAS PubMed Google Scholar
• Zorick, T. S., Syroid, D. E., Brown, A., Gridley, T. & Lemke, G. Krox-20 controls SCIP expression, cell cycle exit and susceptibility to apoptosis in developing myelinating Schwann cells. Development 126, 1397–1406 (1999).
  CAS PubMed Google Scholar
• Musso, M., Balestra, P., Taroni, F., Bellone, E. & Mandich, P. Different consequences of EGR2 mutants on the transactivation of human cx32 promoter. Neurobiol. Dis. 12, 89–95 (2003).
  Article CAS PubMed Google Scholar
• Warner, L. E., Svaren, J., Milbrandt, J. & Lupski, J. R. Functional consequences of mutations in the early growth response 2 gene (EGR2) correlate with severity of human myelinopathies. Hum. Mol. Genet. 8, 1245–1251 (1999).
  Article CAS PubMed Google Scholar
• Peirano, R. I., Goerich, D. E., Riethmacher, D. & Wegner, M. Protein zero gene expression is regulated by the glial transcription factor Sox10. Mol. Cell. Biol. 20, 3198–3209 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Bondurand, N. et al. 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 (2001). A CMTX-associated mutation in the Cx32 promoter abolishes its normal activation by SOX10. This links the two proteins in a common functional pathway that is disrupted in some neuropathies.
  Article CAS PubMed Google Scholar
• Paratore, C., Eichenberger, C., Suter, U. & Sommer, L. Sox10 haploinsufficiency affects maintenance of progenitor cells in a mouse model of Hirschsprung disease. Hum. Mol. Genet. 11, 3075–3085 (2002).
  Article CAS PubMed Google Scholar
• Kim, J., Lo, L., Dormand, E. & Anderson, D. J. SOX10 maintains multipotency and inhibits neuronal differentiation of neural crest stem cells. Neuron 38, 17–31 (2003).
  Article CAS PubMed Google Scholar
• Stolt, C. C. et al. Terminal differentiation of myelin-forming oligodendrocytes depends on the transcription factor Sox10. Genes Dev. 16, 165–170 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Britsch, S. et al. The transcription factor Sox10 is a key regulator of peripheral glial development. Genes Dev. 15, 66–78 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Zhao, C. et al. Charcot–Marie–Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bβ. Cell 105, 587–597 (2001).
  Article CAS PubMed Google Scholar
• Hirokawa, N. Kinesin and dynein superfamily proteins and the mechanism of organelle transport. Science 279, 519–526 (1998).
  Article CAS PubMed Google Scholar
• Mok, H. et al. Association of the kinesin superfamily motor protein KIF1Bα with postsynaptic density-95 (PSD-95), synapse-associated protein-97, and synaptic scaffolding molecule PSD-95/discs large/zona occludens-1 proteins. J. Neurosci. 22, 5253–5258 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Griffin, J. W. & Watson, D. F. Axonal transport in neurologic disease. Ann. Neurol. 23, 3–13 (1988).
  Article CAS PubMed Google Scholar
• Zhu, Q., Couillard-Despres, S. & Julien, J. P. Delayed maturation of regenerating myelinated axons in mice lacking neurofilaments. Exp. Neurol. 148, 299–316 (1997).
  Article CAS PubMed Google Scholar
• Lee, M. K., Marzalek, J. R. & Cleveland, D. W. A mutant neurofilament subunit causes massive, selective motor neuron death: implications for the pathogenesis of human motor neuron disease. Neuron 13, 975–988 (1994).
  Article CAS PubMed Google Scholar
• Ohara, O., Gahara, Y., Miyake, T., Teraoka, H. & Kitamura, T. Neurofilament deficiency in quail caused by nonsense mutation in neurofilament-L gene. J. Cell Biol. 121, 387–395 (1993).
  Article CAS PubMed Google Scholar
• Brownlees, J. et al. Charcot–Marie–Tooth disease neurofilament mutations disrupt neurofilament assembly and axonal transport. Hum. Mol. Genet. 11, 2837–2844 (2002).
  Article CAS PubMed Google Scholar
• Perez-Olle, R., Leung, C. L. & Liem, R. K. H. Effects of Charcot–Marie–Tooth-linked mutations of the neurofilament light subunit on intermediate filament formation. J. Cell Sci. 115, 4937–4946 (2002). Together, references 120 and 121 show that mutant NEFL proteins do not properly form intermediate filaments, have dominant effects on the assembly of wild-type neurofilaments and disrupt the axonal transport of neurofilaments.
  Article CAS PubMed Google Scholar
• Al-Chalabi, A. & Miller, C. C. Neurofilaments and neurological disease. Bioessays 25, 346–355 (2003).
  Article CAS PubMed Google Scholar
• Crosby, A. H. & Proukakis, C. Is the transportation highway the right road for hereditary spastic paraplegia? Am. J. Hum. Genet. 71, 1009–1016 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Reid, E. et al. A kinesin heavy chain (KIF5A) mutation in hereditary spastic paraplegia (SPG10). Am. J. Hum. Genet. 71, 1189–1194 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Xia, C. H. et al. Abnormal neurofilament transport caused by targeted disruption of neuronal kinesin heavy chain KIF5A. J. Cell Biol. 161, 55–66 (2003). Mice lacking neuronal KIF5A have greatly diminished transport of neurofilaments.
  Article CAS PubMed PubMed Central Google Scholar
• LaMonte, B. H. et al. Disruption of dynein/dynactin inhibits axonal transport in motor neurons causing late-onset porgressive degeneration. Neuron 34, 715–727 (2002).
  Article CAS PubMed Google Scholar
• Puls, I. et al. Mutant dynactin in motor neuron disease. Nature Genet. 33, 455–456 (2003). A mutation in the p150 dynactin subunit causes motor neuron disease; the corresponding mutant protein has decreased binding to microtubules.
  Article CAS PubMed Google Scholar
• Bomont, P. et al. The gene encoding gigaxonin, a new member of the cytoskeletal BTB/kelch repeat family, is mutated in giant axonal neuropathy. Nature Genet. 26, 370–374 (2000).
  Article CAS PubMed Google Scholar
• Ding, J. Q. et al. Microtubule-associated protein 1B: a neuronal binding partner for gigaxonin. J. Cell Biol. 158, 427–433 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Auer-Grumbach, M. et al. Autosomal dominant inherited neuropathies with prominent sensory loss and mutilations: a review. Arch. Neurol. 60, 329–334 (2003).
  Article PubMed Google Scholar
• Echard, A. et al. Interaction of a Golgi-associated kinesin-like protein with Rab6. Science 279, 580–585 (1998).
  Article CAS PubMed Google Scholar
• Cantalupo, G., Alifano, P., Roberti, V., Bruni, C. B. & Bucci, C. Rab-interacting lysosomal protein (RILP): the Rab7 effector required for transport to lysosomes. EMBO J. 20, 683–693 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Jordens, I. et al. The Rab7 effector protein RILP controls lysosomal transport by inducing the recruitment of dynein–dynactin motors. Curr. Biol. 11, 1680–1685 (2001).
  Article CAS PubMed Google Scholar
• Verhoeven, K. et al. Mutations in the small GTP-ase late endosomal protein RAB7 cause Charcot–Marie–Tooth disease type 2B neuropathy. Am. J. Hum. Genet. 72 (2003).
• Choudhury, A. et al. Rab proteins mediate Golgi transport of caveola-internalized glycosphingolipids and correct lipid trafficking in Niemann–Pick C cells. J. Clin. Invest. 109, 1541–1550 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Ostlund, C. & Worman, H. J. Nuclear envelope proteins and neuromuscular diseases. Muscle Nerve 27, 393–406 (2003).
  Article CAS PubMed Google Scholar
• Eriksson, M. et al. Recurrent de novo point mutations in lamin A cause Hutchinson–Gilford progeria syndrome. Nature 429, 293–298 (2003).
  Article CAS Google Scholar
• Sullivan, T. et al. Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy. J. Cell Biol. 147, 913–920 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Antonellis, A. et al. Glycyl tRNA synthetase mutations in Charcot–Marie–Tooth disease type 2D and distal spinal muscular atrophy type V. Am. J. Hum. Genet. 72, 1293–1299 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Freist, W., Logan, D. T. & Gauss, D. H. Glycyl-tRNA synthetase. Biol. Chem. Hoppe Seyler 377, 343–56 (1996).
  CAS PubMed Google Scholar
• Martini, R. The effect of myelinating Schwann cells on axons. Muscle Nerve 24, 456–466 (2001).
  Article CAS PubMed Google Scholar
• Peles, E. & Salzer, J. L. Molecular domains of myelinated fibers. Curr. Opin. Neurobiol. 10, 558–565 (2000).
  Article CAS PubMed Google Scholar
• Lappe-Siefke, C. et al. Disruption of Cnp1 uncouples oligodendroglial functions in axonal support and myelination. Nature Genet. 33, 366–374 (2003). Axonal pathologies are the only defect in mice lacking the myelin-related protein CNP, which is not expressed by neurons. This indicates that secondary axonal damage can occur without morphologically detectable effects in myelinating glia.
  Article CAS PubMed Google Scholar
• Mäurer, M. et al. Role of immune cells in animal models for inherited neuropathies: facts and visions. J. Anat. 200, 405–414 (2002).
  Article PubMed PubMed Central Google Scholar
• Sancho, S., Magyar, J. P., Aguzzi, A. & Suter, U. Distal axonopathy in peripheral nerves of PMP22 mutant mice. Brain 122, 1563–1577 (1999). The number of large, myelinated axons is reduced in a length-dependent pattern in Pmp22 mutant mice, demonstrating axonopathy in a genetically authentic animal model of a demyelinating neuropathy.
  Article PubMed Google Scholar
• Perea, J. et al. Induced myelination and demyelination in a conditional mouse model of Charcot–Marie–Tooth disease type 1A. Hum. Mol. Genet. 10, 1007–1018 (2001). Demyelination in adult mice can be induced by overexpressing Pmp22 in myelinating Schwann cells. Conversely, normalizing Pmp22 expression in diseased Schwann cells increases the degree of remyelination, indicating that some of the defects are reversible.
  Article CAS PubMed Google Scholar
• Samsam, M. et al. The Wld S mutation delays robust loss of motor and sensory axons in a genetic model for myelin-related axonopathy. J. Neurosci. 23, 2833–2839 (2003). The neuronal expression of a chimeric protein that delays Wallerian degeneration delays axonal loss in Mpz −/− mice. This provides proof-of-principle that axonal loss can be ameliorated in an animal model.
  Article CAS PubMed PubMed Central Google Scholar