Proteolipid Protein Modulates Preservation of Peripheral Axons and Premature Death when Myelin Protein Zero is Lacking

2016 | journal article. A publication with affiliation to the University of Göttingen.

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​Proteolipid Protein Modulates Preservation of Peripheral Axons and Premature Death when Myelin Protein Zero is Lacking​
Patzig, J.; Kusch, K.; Fledrich, R.; Eichel, M. A.; Lueders, K. A.; Möbius, W.   & Sereda, M. W. et al.​ (2016) 
Glia64(1) pp. 155​-174​.​ DOI: 

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Patzig, Julia; Kusch, Kathrin; Fledrich, Robert; Eichel, Maria A.; Lueders, Katja A.; Möbius, Wiebke ; Sereda, Michael W.; Nave, Klaus-Armin; Martini, Rudolf; Werner, Hauke B.
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 star) Plp(null)-double-mutant mice. Compared with either single-mutant, P0(null star) 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 star) 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.
Issue Date
1098-1136; 0894-1491



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