Highlights
- •PMP22 may lead to various kinds of peripheral neuropathy in humans.
- •Many rodent models of PMP22-related peripheral neuropathies (PMP22-PN) have been developed.
- •Specific pathological hallmarks have been observed in both animals and humans.
- •Additional correlations between PMP22 animal models and PMP22-PN may be helpful to rationalize the development of efficient drugs in CMT.
Abstract
Background
Charcot-Marie-Tooth diseases (CMT) are due to abnormalities of many genes, the most
frequent being linked to PMP22 (Peripheral Myelin Protein 22). In the past, only spontaneous genetic anomalies occurring
in mouse mutants such as Trembler (Tr) mice were available; more recently, several
rodent models have been generated for exploration of the pathophysiological mechanisms
underlying these neuropathies.
Methods
Based on the personal experience of our team, we describe here the pathological hallmarks
of most of these animal models and compare them to the pathological features observed
in some CMT patient nerves (CMT types 1A and E; hereditary neuropathy with liability
to pressure palsies, HNPP).
Results
We describe clinical data and detailed pathological analysis mainly by electron microscopy
of the sciatic nerves of these animal models conducted in our laboratory; lesions
of PMP22 deficient animals (KO and mutated PMP22) and PMP22 overexpressed models are described and compared to ultrastructural anomalies
of nerve biopsies from CMT patients due to PMP22 gene anomalies. It is of note that while there are some similarities, there are also
significant differences between the lesions in animal models and human cases. Such
observations highlight the complex roles played by PMP22 in nerve development.
Conclusion
It should be borne in mind that we require additional correlations between animal
models of hereditary neuropathies and CMT patients to rationalize the development
of efficient drugs.
Keywords
Abbreviations:
AA (ascorbic acid), AD (autosomal dominant), CMT (Charcot-Marie-Tooth disease), CMTde (dysmyelinating form of CMT), CHN (Congenital Hypomyelinating Neuropathy), CNS (central nervous system), dup (duplication), DNA (deoxyribonucleic acid), DSS (Dejerine-Sottas syndrome), EM (electron microscopy), HNPP (hereditary neuropathy with liability to pressure palsies), HSP70 (heat shock protein 70), KO (knock out), MPZ (myelin protein zero (P0)), mRNA (messenger ribonucleic acid), NC (nerve conduction), PMP22 (peripheral myelin protein 22), PNS (peripheral nervous system), SC (Schwann cell), TgN (transgenic), TM (transmembrane domain), Tr (trembler), Tr-J (trembler J), YAC (yeast artificial chromosome.)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: January 21, 2019
Accepted:
January 16,
2019
Received in revised form:
December 26,
2018
Received:
August 3,
2018
Identification
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© 2019 Elsevier B.V. All rights reserved.
