Brain, Vol. 122, No. 8, 1563-1577,
August 1999
© 1999 Oxford University Press
Distal axonopathy in peripheral nerves of PMP22-mutant mice
1 Department of Cell Biology, Swiss Federal Institute of Technology and 2 Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland
Correspondence to:
Professor Dr Ueli Suter, Institute of Cell Biology, Swiss Federal Institute of Technology, ETH-Hoenggerberg, CH-8093 Zurich, Switzerland E-mail: usuter{at}cell.biol.ethz.ch
A partial duplication of chromosome 17 is associated with Charcot–Marie–Tooth disease type 1A (CMT1A), a demyelinating peripheral neuropathy that causes progressive distal muscle atrophy and sensory impairment. Trisomic expression of peripheral myelin protein 22 (PMP22) whose gene is contained within the duplicated region is considered to be responsible for the disease. By using recombinant gene technology in rodents, we had demonstrated previously that PMP22 is sensitive to gene dosage. Homozygous PMP22 knockout (PMP220/0) mice and transgenic animals carrying additional copies of the PMP22 gene develop distinct peripheral polyneuropathies. We have now performed a detailed morphometrical analysis of the L3 roots, quadriceps and saphenous nerves of these PMP22-mutant mice to study whether the myelin and potential axonal deficits are evenly distributed. The L3 roots and the peripheral nerves were chosen as representatives of the proximal and distal segments of the peripheral nervous system. When the roots were compared with the peripheral nerves, myelin deficiencies appeared more severe at the radicular levels, in particular the ventral roots. Decreased numbers of large calibre axons were a prominent feature in the motor branches of both strains of PMP22-mutant mice, and these axonal deficits were more severe distally. Active axonal damage was only observed in the nerves of PMP220/0 mice. Despite the distinct effects on myelination and the Schwann cell phenotype that characterize the neuropathies of PMP22-mutant mice, both strains develop a distally accentuated axonopathy as a common disease mechanism which is likely to be responsible for the neurological deficits.
Charcot-Marie-Tooth disease; Peripheral myelin protien 22; Knockout mice; axonal atrophy
CMT = Charcot-Maire-Tooth disease; Cx32 = connexin32; HMSN = hereditary motor and sensory neuropathy; HNPP = hereditary neuropathy with liability to pressure plasies; NF = neurofilaments; PLP = proteolipid protein; PMP22 = periheral myelin protein 22; P0 = protein zero; Tr = Trembler
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  X. Yin, G. J. Kidd, E. P. Pioro, J. McDonough, R. Dutta, M. L. Feltri, L. Wrabetz, A. Messing, R. M. Wyatt, R. J. Balice-Gordon, et al. Dysmyelinated Lower Motor Neurons Retract and Regenerate Dysfunctional Synaptic Terminals J. Neurosci., April 14, 2004; 24(15): 3890 - 3898. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Hattori, M. Yamamoto, T. Yoshihara, H. Koike, M. Nakagawa, H. Yoshikawa, A. Ohnishi, K. Hayasaka, O. Onodera, M. Baba, et al. Demyelinating and axonal features of Charcot-Marie-Tooth disease with mutations of myelin-related proteins (PMP22, MPZ and Cx32): a clinicopathological study of 205 Japanese patients Brain, January 1, 2003; 126(1): 134 - 151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Robaglia-Schlupp, J. Pizant, J.-C. Norreel, E. Passage, D. Saberan-Djoneidi, J.-L. Ansaldi, L. Vinay, D. Figarella-Branger, N. Levy, F. Clarac, et al. PMP22 overexpression causes dysmyelination in mice Brain, October 1, 2002; 125(10): 2213 - 2221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sancho, P. Young, and U. Suter Regulation of Schwann cell proliferation and apoptosis in PMP22-deficient mice and mouse models of Charcot-Marie-Tooth disease type 1A Brain, November 1, 2001; 124(11): 2177 - 2187. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Krajewski, R. A. Lewis, D. R. Fuerst, C. Turansky, S. R. Hinderer, J. Garbern, J. Kamholz, and M. E. Shy Neurological dysfunction and axonal degeneration in Charcot-Marie-Tooth disease type 1A Brain, July 1, 2000; 123(7): 1516 - 1527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Niemann, M. W. Sereda, U. Suter, I. R. Griffiths, and K.-A. Nave Uncoupling of Myelin Assembly and Schwann Cell Differentiation by Transgenic Overexpression of Peripheral Myelin Protein 22 J. Neurosci., June 1, 2000; 20(11): 4120 - 4128. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Wrabetz, M. L. Feltri, A. Quattrini, D. Imperiale, S. Previtali, M. D'Antonio, R. Martini, X. Yin, B. D. Trapp, L. Zhou, et al. P0 Glycoprotein Overexpression Causes Congenital Hypomyelination of Peripheral Nerves J. Cell Biol., March 6, 2000; 148(5): 1021 - 1034. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kamholz, D. Menichella, A. Jani, J. Garbern, R. A. Lewis, K. M. Krajewski, J. Lilien, S. S. Scherer, and M. E. Shy Charcot-Marie-Tooth disease type 1: Molecular pathogenesis to gene therapy Brain, February 1, 2000; 123(2): 222 - 233. [Abstract] [Full Text] [PDF]
|
|