PMP22 transgenic dorsal root ganglia cultures show myelin abnormalities similar to those of human CMT1A

Lucilla Nobbio, Gianluigi Mancardi, Marina Grandis, Giovanni Levi, Ueli Suter, Klaus Armin Nave, Anthony John Windebank, Michele Abbruzzese, Angelo Schenone

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Charcot-Marie-Tooth 1A (CMT1A) neuropathy is caused by duplication of the peripheral myelin protein 22 (PMP22) gene, leading to protein overexpression. Although this protein has a role in regulating Schwann cell growth and peripheral myelin compaction, how altered concentrations of PMP22 impair myelination is unknown. We established dorsal root ganglia (DRG) cultures from a transgenic rat overexpressing PMP22 (PMP22tg) to study the behavior of PMP22tg Schwann cells in early stages of development and myelination. We used reverse transcriptase-polymerase chain reaction and light and electron microscopy to study PMP22 expression and myelin formation. Myelin ultrastructure was evaluated in sural nerves from CMT1A patients to compare experimental and human findings. PMP22tg DRG cultures contained a greater number of internodes devoid of myelin, in the absence of remyelination, and increased periodicity of myelin lamellae compared with normal cultures. Widening of myelin lamellae was also observed in CMT1A biopsy specimens. Our results suggest that both functions of PMP22, in regulating Schwann cell differentiation and contributing to peripheral myelin compaction, are affected by its overexpression. The presence of similar myelin abnormalities in PMP22tg cultures and human nerves emphasizes the importance of developing in vitro models of hereditary neuropathies to study their underlying pathomechanisms.

Original languageEnglish (US)
Pages (from-to)47-55
Number of pages9
JournalAnnals of Neurology
Volume50
Issue number1
DOIs
StatePublished - 2001

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Myelin Proteins
Spinal Ganglia
Myelin Sheath
Tooth
Schwann Cells
Transgenic Rats
Sural Nerve
Periodicity
Reverse Transcriptase Polymerase Chain Reaction
Cell Differentiation
Electron Microscopy
Proteins
Biopsy
Light

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Nobbio, L., Mancardi, G., Grandis, M., Levi, G., Suter, U., Nave, K. A., ... Schenone, A. (2001). PMP22 transgenic dorsal root ganglia cultures show myelin abnormalities similar to those of human CMT1A. Annals of Neurology, 50(1), 47-55. https://doi.org/10.1002/ana.1034

PMP22 transgenic dorsal root ganglia cultures show myelin abnormalities similar to those of human CMT1A. / Nobbio, Lucilla; Mancardi, Gianluigi; Grandis, Marina; Levi, Giovanni; Suter, Ueli; Nave, Klaus Armin; Windebank, Anthony John; Abbruzzese, Michele; Schenone, Angelo.

In: Annals of Neurology, Vol. 50, No. 1, 2001, p. 47-55.

Research output: Contribution to journalArticle

Nobbio, L, Mancardi, G, Grandis, M, Levi, G, Suter, U, Nave, KA, Windebank, AJ, Abbruzzese, M & Schenone, A 2001, 'PMP22 transgenic dorsal root ganglia cultures show myelin abnormalities similar to those of human CMT1A', Annals of Neurology, vol. 50, no. 1, pp. 47-55. https://doi.org/10.1002/ana.1034
Nobbio, Lucilla ; Mancardi, Gianluigi ; Grandis, Marina ; Levi, Giovanni ; Suter, Ueli ; Nave, Klaus Armin ; Windebank, Anthony John ; Abbruzzese, Michele ; Schenone, Angelo. / PMP22 transgenic dorsal root ganglia cultures show myelin abnormalities similar to those of human CMT1A. In: Annals of Neurology. 2001 ; Vol. 50, No. 1. pp. 47-55.
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