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Gene Review

Mpz  -  myelin protein zero

Mus musculus

Synonyms: MPP, Mpp, Myelin peripheral protein, Myelin protein P0, Myelin protein zero, ...
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Disease relevance of Mpz

  • In cultures of dissociated cells of embryonic rat DRG, where we knocked-down the C/EBP-delta mRNA, we found an inhibition of P0 mRNA induction by IL6RIL6, showing that the role of C/EBP-delta on this myelin gene is not unique to the melanoma system [1].
  • Relapsing lesions, characterized by demyelination of areas previously remyelinated by Schwann cells, were studied for differences in the distribution of P0 and MAG [2].
  • Immunocytochemical localization of MAG, MBP and P0 protein in acute and relapsing demyelinating lesions of Theiler's virus infection [2].
  • Wild-type Schwann cells infected with Sox2 adenovirus or lentivirus inhibited expression of myelination-associated genes (e.g., myelin protein zero; Mpz), and failed to myelinate axons in vitro, but had an enhanced proliferative response to beta-neuregulin [3].
  • Mutations in the human gene for the myelin recognition molecule protein zero (P0) give rise to severe and progressive forms of dominantly inherited peripheral neuropathies [4].

High impact information on Mpz

  • These results demonstrate that P0 is essential for the normal spiraling, compaction, and maintenance of the peripheral myelin sheath and the continued integrity of associated axons [5].
  • Mouse P0 gene disruption leads to hypomyelination, abnormal expression of recognition molecules, and degeneration of myelin and axons [5].
  • In conclusion, P0 and the proteolipid proteins are evolving in parallel in myelinating cells of most vertebrate species [6].
  • Vertebrate myelin contains two proteins that mediate compaction: protein zero (P0), an immunoglobulin gene superfamily member, or proteolipid proteins, 4-hydrophobic domain-motif proteins biogenetically unrelated to P0 [6].
  • In secondary Schwann cells, both T antigen and c-Jun are required for significant inhibition of the P0 promoter; expression of only one of the proteins is insufficient for repression of the P0 gene [7].

Biological context of Mpz

  • To test this directly, we produced mice in which either the MpzS63C (DSS) or MpzS63del (CMT1B) transgene was inserted randomly, so that the endogenous Mpz alleles could compensate for any loss of mutant P0 function [8].
  • Analysis of Southern blots of DNA obtained from these hybrids allows us to unambiguously assign the P0 gene to mouse chromosome 1 [9].
  • The down-regulation of Pax3, also typical of the transition to myelinating cells, was observed after C/EBP-delta expression in correlation to P0 induction and to decrease of melanogenesis and cell growth [1].
  • Similar to the rat gene, the mouse P0 gene is encoded by six exons that span about 7 kb of DNA [10].
  • Both cell types appear to influence each other mutually, i.e., impaired T lymphocyte development in RAG-1-deficient P0 mutants leads to decreased macrophage numbers and retarded macrophage activation causes reduced T lymphocyte numbers in the peripheral nerves of P0(+/-) mice [11].

Anatomical context of Mpz


Associations of Mpz with chemical compounds

  • Doxycycline-regulated overexpression of C/EBP-delta was sufficient to induce accumulation of P0 and MBP mRNAs, the effect being selective, because C/EBP-delta did not affect several other genes strongly regulated by IL6RIL6 [1].
  • By contrast, the concentrations of P0 glycoprotein and myelin basic proteins were reduced to 27% and 20% of control levels, respectively [15].
  • The comparison with rat P0 sequence revealed, besides a Lys172 to Arg substitution, that in the first peptide, two serine residues (Ser176 and Ser181) were phosphorylated, Ser176 appearing to be modified subsequently to Ser181 [16].
  • In situ hybridization of biotin-labeled P0 rat cDNA probe to chromosome spreads and detection of specific signal with fluorescein isothiocyanate-conjugated avidin revealed a strong signal on the 1(14) translocation chromosome at the site of the breakpoint [17].
  • According to the liquid model for interparticle interference from charged spheres, the 80 A-diameter particle has 10 negative surface charges which likely arise from negatively charged SDS molecules bound to the transmembrane domain of P0 [18].

Regulatory relationships of Mpz

  • We therefore cross-bred the P0+/- mice with spontaneous osteopetrotic (op) mutants deficient in the macrophage colony-stimulating factor (M-CSF), hence displaying impaired macrophage activation [14].
  • We show that MAG-deficient Schwann cells do myelinate DRG neurons in vitro and express the myelin-specific glycolipid galactocerebroside (Gal-C) and the myelin proteins P0 and MBP [19].

Other interactions of Mpz


Analytical, diagnostic and therapeutic context of Mpz

  • Densitometric analysis of Northern blots showed that, in normal mice, the proportion of P0 mRNA increases up to the 12th day, then decreases slowly [13].
  • Using immunological techniques, we show that, as early as postnatal day 8, the P0 content of mice homozygous and heterozygous for the Trembler mutation, represent respectively one tenth and half of the normal values [25].
  • Mice heterozygously deficient in the p0 gene (P0(+/-)) are animal models for some forms of inherited neuropathies [22].
  • We show that P0 mRNA transcripts are expressed in thymic stroma, similar to other myelin proteins and that expression of intact P0 protein can be detected by Western blot [26].
  • DNA sequence conservation within the 5' regions of the human, mouse, and rat P0 genes correlates closely with the results of promoter deletion analysis of the 1.1-kilobase pair region assayed in Schwann cell cultures and reveals a potent proximal region from position -350 to +45 [27].


  1. C/EBP-delta induction by gp130 signaling. Role in transition to myelin gene expressing phenotype in a melanoma cell line model. Kamaraju, A.K., Adjalley, S., Zhang, P., Chebath, J., Revel, M. J. Biol. Chem. (2004) [Pubmed]
  2. Immunocytochemical localization of MAG, MBP and P0 protein in acute and relapsing demyelinating lesions of Theiler's virus infection. Dal Canto, M.C., Barbano, R.L. J. Neuroimmunol. (1985) [Pubmed]
  3. Analysis of congenital hypomyelinating Egr2Lo/Lo nerves identifies Sox2 as an inhibitor of Schwann cell differentiation and myelination. Le, N., Nagarajan, R., Wang, J.Y., Araki, T., Schmidt, R.E., Milbrandt, J. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  4. Protein zero (P0)-deficient mice show myelin degeneration in peripheral nerves characteristic of inherited human neuropathies. Martini, R., Zielasek, J., Toyka, K.V., Giese, K.P., Schachner, M. Nat. Genet. (1995) [Pubmed]
  5. Mouse P0 gene disruption leads to hypomyelination, abnormal expression of recognition molecules, and degeneration of myelin and axons. Giese, K.P., Martini, R., Lemke, G., Soriano, P., Schachner, M. Cell (1992) [Pubmed]
  6. Parallel evolution and coexpression of the proteolipid proteins and protein zero in vertebrate myelin. Yoshida, M., Colman, D.R. Neuron (1996) [Pubmed]
  7. SV40 large T antigen with c-Jun down-regulates myelin P0 gene expression: a mechanism for papovaviral T antigen-mediated demyelination. Bharucha, V.A., Peden, K.W., Tennekoon, G.I. Neuron (1994) [Pubmed]
  8. Different intracellular pathomechanisms produce diverse Myelin Protein Zero neuropathies in transgenic mice. Wrabetz, L., D'Antonio, M., Pennuto, M., Dati, G., Tinelli, E., Fratta, P., Previtali, S., Imperiale, D., Zielasek, J., Toyka, K., Avila, R.L., Kirschner, D.A., Messing, A., Feltri, M.L., Quattrini, A. J. Neurosci. (2006) [Pubmed]
  9. The gene encoding peripheral myelin protein zero is located on mouse chromosome 1. Kuhn, R., Pravtcheva, D., Ruddle, F., Lemke, G. J. Neurosci. (1990) [Pubmed]
  10. DNA sequence, genomic organization, and chromosomal localization of the mouse peripheral myelin protein zero gene: identification of polymorphic alleles. You, K.H., Hsieh, C.L., Hayes, C., Stahl, N., Francke, U., Popko, B. Genomics (1991) [Pubmed]
  11. Attenuated demyelination in the absence of the macrophage-restricted adhesion molecule sialoadhesin (Siglec-1) in mice heterozygously deficient in P0. Kobsar, I., Oetke, C., Kroner, A., Wessig, C., Crocker, P., Martini, R. Mol. Cell. Neurosci. (2006) [Pubmed]
  12. Mice doubly deficient in the genes for P0 and myelin basic protein show that both proteins contribute to the formation of the major dense line in peripheral nerve myelin. Martini, R., Mohajeri, M.H., Kasper, S., Giese, K.P., Schachner, M. J. Neurosci. (1995) [Pubmed]
  13. Developmental expression of the P0 glycoprotein and basic protein mRNAs in normal and trembler mutant mice. Garbay, B., Domec, C., Fournier, M., Bonnet, J. J. Neurochem. (1989) [Pubmed]
  14. Role of immune cells in animal models for inherited neuropathies: facts and visions. Mäurer, M., Kobsar, I., Berghoff, M., Schmid, C.D., Carenini, S., Martini, R. J. Anat. (2002) [Pubmed]
  15. Myelin-associated glycoprotein and other proteins in Trembler mice. Inuzuka, T., Quarles, R.H., Heath, J., Trapp, B.D. J. Neurochem. (1985) [Pubmed]
  16. Myelin P0 glycoprotein: identification of the site phosphorylated in vitro and in vivo by endogenous protein kinases. Hilmi, S., Fournier, M., Valeins, H., Gandar, J.C., Bonnet, J. J. Neurochem. (1995) [Pubmed]
  17. Induced reciprocal translocation in transgenic mice near sites of transgene integration. Francke, U., Hsieh, C.L., Kelly, D., Lai, E., Popko, B. Mamm. Genome (1992) [Pubmed]
  18. Tetrameric assembly of full-sequence protein zero myelin glycoprotein by synchrotron x-ray scattering. Inouye, H., Tsuruta, H., Sedzik, J., Uyemura, K., Kirschner, D.A. Biophys. J. (1999) [Pubmed]
  19. MAG-deficient Schwann cells myelinate dorsal root ganglion neurons in culture. Carenini, S., Montag, D., Schachner, M., Martini, R. Glia (1998) [Pubmed]
  20. Absence of P0 leads to the dysregulation of myelin gene expression and myelin morphogenesis. Xu, W., Manichella, D., Jiang, H., Vallat, J.M., Lilien, J., Baron, P., Scarlato, G., Kamholz, J., Shy, M.E. J. Neurosci. Res. (2000) [Pubmed]
  21. Subtle roles of neural cell adhesion molecule and myelin-associated glycoprotein during Schwann cell spiralling in P0-deficient mice. Carenini, S., Montag, D., Schachner, M., Martini, R. Glia (1999) [Pubmed]
  22. The role of macrophages in demyelinating peripheral nervous system of mice heterozygously deficient in p0. Carenini, S., Mäurer, M., Werner, A., Blazyca, H., Toyka, K.V., Schmid, C.D., Raivich, G., Martini, R. J. Cell Biol. (2001) [Pubmed]
  23. Nerve conduction abnormalities in aging mice deficient for myelin-associated glycoprotein. Weiss, M.D., Luciano, C.A., Quarles, R.H. Muscle Nerve (2001) [Pubmed]
  24. Pathogenesis of axonal dystrophy and demyelination in alphaA-crystallin-expressing transgenic mice. Van Rijk, A.F., Sweers, M.A., Merkx, G.F., Lammens, M., Bloemendal, H. International journal of experimental pathology. (2003) [Pubmed]
  25. P0 protein in normal, trembler heterozygous/homozygous mice during active PNS myelination. Garbay, B., Bonnet, J. Neuroreport (1992) [Pubmed]
  26. Tolerance induction by intrathymic expression of P0. Visan, L., Visan, I.A., Weishaupt, A., Hofstetter, H.H., Toyka, K.V., Hünig, T., Gold, R. J. Immunol. (2004) [Pubmed]
  27. Multiple regulatory elements control transcription of the peripheral myelin protein zero gene. Brown, A.M., Lemke, G. J. Biol. Chem. (1997) [Pubmed]
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