Abstract |
Protein zero (P0) is the major structural component of peripheral myelin. Lack of this adhesion protein from Schwann cells causes a severe dysmyelinating neuropathy with secondary axonal degeneration in humans with the neuropathy Dejerine-Sottas syndrome (DSS) and in the corresponding mouse model (P0(null)-mice). In the mammalian CNS, the tetraspan- membrane protein PLP is the major structural myelin constituent and required for the long-term preservation of myelinated axons, which fails in hereditary spastic paraplegia (SPG type-2) and the relevant mouse model (Plp(null)-mice). The Plp-gene is also expressed in Schwann cells but PLP is of very low abundance in normal peripheral myelin; its function has thus remained enigmatic. Here we show that the abundance of PLP but not of other tetraspan myelin proteins is strongly increased in compact peripheral myelin of P0(null)-mice. To determine the functional relevance of PLP expression in the absence of P0, we generated P0(null)*Plp(null)-double-mutant mice. Compared with either single-mutant, P0(null)*Plp(null)-mice display impaired nerve conduction, reduced motor functions, and premature death. At the morphological level, axonal segments were frequently non-myelinated but in a one-to-one relationship with a hypertrophic Schwann cell. Importantly, axonal numbers were reduced in the vital phrenic nerve of P0(null)*Plp(null)-mice. In the absence of P0, thus, PLP also contributes to myelination by Schwann cells and to the preservation of peripheral axons. These data provide a link between the Schwann cell-dependent support of peripheral axons and the oligodendrocyte-dependent support of central axons.
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Authors | Julia Patzig, Kathrin Kusch, Robert Fledrich, Maria A Eichel, Katja A Lüders, Wiebke Möbius, Michael W Sereda, Klaus-Armin Nave, Rudolf Martini, Hauke B Werner |
Journal | Glia
(Glia)
Vol. 64
Issue 1
Pg. 155-74
(Jan 2016)
ISSN: 1098-1136 [Electronic] United States |
PMID | 26393339
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2015 Wiley Periodicals, Inc. |
Chemical References |
- Mag protein, mouse
- Mpz protein, mouse
- Myelin P0 Protein
- Myelin Proteolipid Protein
- Myelin-Associated Glycoprotein
- Plp1 protein, mouse
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Topics |
- Animals
- Axons
(metabolism, pathology)
- Brain
(metabolism, pathology)
- Female
- Kaplan-Meier Estimate
- Mice, Inbred C57BL
- Mice, Knockout
- Mortality, Premature
- Motor Activity
(physiology)
- Myelin P0 Protein
(genetics, metabolism)
- Myelin Proteolipid Protein
(genetics, metabolism)
- Myelin Sheath
(metabolism, pathology)
- Myelin-Associated Glycoprotein
(metabolism)
- Neural Conduction
(physiology)
- Optic Nerve
(metabolism, pathology)
- Phrenic Nerve
(metabolism, pathology)
- Sciatic Nerve
(metabolism, pathology)
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