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Gene Review

Plp1  -  proteolipid protein (myelin) 1

Mus musculus

Synonyms: DM20, Lipophilin, Myelin proteolipid protein, PLP, Plp, ...
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Disease relevance of Plp1


Psychiatry related information on Plp1

  • Jimpy mice spent less time engaged in coordinated motor activities (locomotion and grooming) than normal littermates, and more time engaged in slight movement or remaining inactive [6].

High impact information on Plp1

  • Recently we have found that unmanipulated SJL mice that are highly susceptible to EAE also maintain a very high frequency of T cells responding to an encephalitogenic epitope of a myelin antigen proteolipid protein (PLP) 139-151 in the peripheral repertoire [7].
  • Based on the PLP 139-151 system, we propose a model in which activation with foreign antigens can result in the generation of pathogenic memory T cells that mediate autoimmunity [7].
  • This is not due to lack of expression of myelin antigens in the thymus resulting in escape of PLP 139-151 reactive cells from central tolerance, but is due to expression of a splice variant of PLP named DM20, which lacks the residues 116-150 [7].
  • On the other hand, connatal PMD mutations lead to the accumulation of both mutant PLP and DM20 proteins in the ER of COS-7 cells with little of either isoform transported to the cell surface [8].
  • We report a cellular basis for the distinction between two disease subtypes, classical and connatal, based on protein trafficking of the two PLP gene products (PLP and DM20) [8].

Chemical compound and disease context of Plp1


Biological context of Plp1

  • Finally, we have localized the murine IL-2R gamma gene, Il2rg, to the X chromosome between Rsvp and Plp and demonstrated that a defect in IL-2R gamma is not responsible for the X chromosome-linked xid mutation, which maps to this same region [12].
  • This suggests that the lethal phenotype associated with the majority of PLP gene mutations is a complex combination of loss and gain-of-function effects of a mutant myelin protein [1].
  • Here, we demonstrate that these PLP-minus mice show no pleiotropism as mice carrying point mutations within the PLP gene [13].
  • The core and particular importance of these four residues in PLP 56-70 was confirmed in vitro using amino acid substitution studies [14].
  • These results indicate that the jp, jpmsd, and qk mutations exhibit qualitatively similar phenotypic effects on MBP gene expression but the magnitude of the effect is proportional to the extent of hypomyelination in each mutant [15].

Anatomical context of Plp1


Associations of Plp1 with chemical compounds


Physical interactions of Plp1

  • However, under the isotonic condition, PLP binds inositol hexakisphosphate (InsP6) significantly, not inositol 1,3,4,5-tetrakisphosphate [22].
  • This finding rules out the possibility that contaminating F0 ATPase gives rise to the DCCD binding exhibited by PLP and confirms the possibility that PLP has proton channel activity, as suggested by Lin and Lees (1,2) [23].

Regulatory relationships of Plp1

  • MBP mRNA levels remained well below control levels in jp/Y brain polyribosomes throughout early postnatal development [24].
  • We have found that steroids, such as glucocorticoids, stimulate the translation of MBP and PLP mRNAs in cell-free systems and inhibit the translation of CNP mRNA [25].
  • Normal and jimpy oligodendrocytes in secondary cultures were transfected with plasmids containing the SV40 T-antigen gene expressed under the control of the mouse metallothionein-I promoter [26].
  • In contrast, no significant difference in GS mRNA content was detected between control and jimpy brain tissue [27].
  • We used compound heterozygote mice to study the long-term fate of oligodendrocytes expressing either the jimpy or rumpshaker allele against a background of cells expressing a Plp-null allele [28].

Other interactions of Plp1

  • At monthly intervals after immunization with p139-151, responses to PLP 249-273, MBP 87-99, and PLP 137-198 were sequentially accumulated in al mice examined [29].
  • Further meiotic mapping in the mouse placed Smcx in the Plp-Pdha1 interval [30].
  • The fine specificity of these epitopes was further investigated using frame-shifted peptides, which indicated cores between MOG 9-15 (GYPIRAL) and PLP 62-68 (NVIHAFQ) [14].
  • OSP/claudin-11 and PLP are both tetraspan proteins concentrated in CNS myelin [31].
  • Immunoblotting analysis did not reveal an increased apparent Mr for MAG in the Jimpy mouse, as has been observed in some other hypomyelinating murine mutants [32].

Analytical, diagnostic and therapeutic context of Plp1

  • PLP was reduced more than the other proteins, as it was not detected by an immunoblotting technique that was capable of detecting 0.5% of the control level [32].
  • Northern blots showed the presence of multiple mouse PLP RNAs, the developmental expression of which coincided with myelination [33].
  • However, MBP and PLP polypeptides could not be detected by western blot or immunocytochemical staining at either the permissive or nonpermissive temperature [34].
  • Immunoelectron microscopy using gold particles showed that the truncated endogenous jimpy PLP was distributed throughout the cytoplasm and in association with the plasma membrane of cell bodies and processes [26].
  • The reverse transplantations (newborn shi or normal into newborn jp brain) demonstrate that the jp environment does not modify the phenotype of normal or shi ODCs [35].


  1. Transgenic and natural mouse models of proteolipid protein (PLP)-related dysmyelination and demyelination. Griffiths, I.R., Schneider, A., Anderson, J., Nave, K.A. Brain Pathol. (1995) [Pubmed]
  2. Regional and developmental variations of GFAP and actin mRNA levels in the CNS of jimpy and shiverer mutant mice. Chen, H., Cabon, F., Sun, P., Parmantier, E., Dupouey, P., Jacque, C., Zalc, B. J. Mol. Neurosci. (1993) [Pubmed]
  3. Distinct phenotypes associated with increasing dosage of the PLP gene: implications for CMT1A due to PMP22 gene duplication. Anderson, T.J., Klugmann, M., Thomson, C.E., Schneider, A., Readhead, C., Nave, K.A., Griffiths, I.R. Ann. N. Y. Acad. Sci. (1999) [Pubmed]
  4. A T cell receptor antagonist peptide induces T cells that mediate bystander suppression and prevent autoimmune encephalomyelitis induced with multiple myelin antigens. Nicholson, L.B., Murtaza, A., Hafler, B.P., Sette, A., Kuchroo, V.K. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  5. Chronic relapsing experimental autoimmune encephalomyelitis with a delayed onset and an atypical clinical course, induced in PL/J mice by myelin oligodendrocyte glycoprotein (MOG)-derived peptide: preliminary analysis of MOG T cell epitopes. Kerlero de Rosbo, N., Mendel, I., Ben-Nun, A. Eur. J. Immunol. (1995) [Pubmed]
  6. The ontogeny of ultrasonic vocalizations and other behaviors in male jimpy (jp/Y) mice and their normal male littermates. Bolivar, V.J., Brown, R.E. Developmental psychobiology. (1994) [Pubmed]
  7. T cell response in experimental autoimmune encephalomyelitis (EAE): role of self and cross-reactive antigens in shaping, tuning, and regulating the autopathogenic T cell repertoire. Kuchroo, V.K., Anderson, A.C., Waldner, H., Munder, M., Bettelli, E., Nicholson, L.B. Annu. Rev. Immunol. (2002) [Pubmed]
  8. A cellular mechanism governing the severity of Pelizaeus-Merzbacher disease. Gow, A., Lazzarini, R.A. Nat. Genet. (1996) [Pubmed]
  9. An altered peptide ligand mediates immune deviation and prevents autoimmune encephalomyelitis. Nicholson, L.B., Greer, J.M., Sobel, R.A., Lees, M.B., Kuchroo, V.K. Immunity (1995) [Pubmed]
  10. Copolymer 1 inhibits chronic relapsing experimental allergic encephalomyelitis induced by proteolipid protein (PLP) peptides in mice and interferes with PLP-specific T cell responses. Teitelbaum, D., Fridkis-Hareli, M., Arnon, R., Sela, M. J. Neuroimmunol. (1996) [Pubmed]
  11. Brain water and electrolytes in response to respiratory acidosis and brain edema in the mutant mouse, jimpy. Nattie, E.E., Sheldon, L. Life Sci. (1982) [Pubmed]
  12. Characterization of cDNAs encoding the murine interleukin 2 receptor (IL-2R) gamma chain: chromosomal mapping and tissue specificity of IL-2R gamma chain expression. Cao, X., Kozak, C.A., Liu, Y.J., Noguchi, M., O'Connell, E., Leonard, W.J. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  13. Adhesive properties of proteolipid protein are responsible for the compaction of CNS myelin sheaths. Boison, D., Büssow, H., D'Urso, D., Müller, H.W., Stoffel, W. J. Neurosci. (1995) [Pubmed]
  14. Encephalitogenic epitopes of myelin basic protein, proteolipid protein, myelin oligodendrocyte glycoprotein for experimental allergic encephalomyelitis induction in Biozzi ABH (H-2Ag7) mice share an amino acid motif. Amor, S., O'Neill, J.K., Morris, M.M., Smith, R.M., Wraith, D.C., Groome, N., Travers, P.J., Baker, D. J. Immunol. (1996) [Pubmed]
  15. Myelin basic protein gene expression in quaking, jimpy, and myelin synthesis-deficient mice. Carnow, T.B., Carson, J.H., Brostoff, S.W., Hogan, E.L. Dev. Biol. (1984) [Pubmed]
  16. An oligodendrocyte-specific zinc-finger transcription regulator cooperates with Olig2 to promote oligodendrocyte differentiation. Wang, S.Z., Dulin, J., Wu, H., Hurlock, E., Lee, S.E., Jansson, K., Lu, Q.R. Development (2006) [Pubmed]
  17. Mutations in the myelin proteolipid protein gene alter oligodendrocyte gene expression in jimpy and jimpymsd mice. Macklin, W.B., Gardinier, M.V., Obeso, Z.O., King, K.D., Wight, P.A. J. Neurochem. (1991) [Pubmed]
  18. His36Pro point-mutated proteolipid protein retained in the endoplasmic reticulum of oligodendrocytes in the shaking pup. Song, J., Goetz, B.D., Duncan, I.D. Glia (2006) [Pubmed]
  19. Myelin basic protein is affected by reduced synthesis of myelin proteolipid protein in the jimpy mouse. Fannon, A.M., Moscarello, M.A. Biochem. J. (1990) [Pubmed]
  20. Studies on NG-methylarginine derivatives in myelin basic protein from developing and mutant mouse brain. Rawal, N., Lee, Y.J., Paik, W.K., Kim, S. Biochem. J. (1992) [Pubmed]
  21. The early phenotype associated with the jimpy mutation of the proteolipid protein gene. Thomson, C.E., Anderson, T.J., McCulloch, M.C., Dickinson, P., Vouyiouklis, D.A., Griffiths, I.R. J. Neurocytol. (1999) [Pubmed]
  22. Myelin proteolipid protein (PLP), but not DM-20, is an inositol hexakisphosphate-binding protein. Yamaguchi, Y., Ikenaka, K., Niinobe, M., Yamada, H., Mikoshiba, K. J. Biol. Chem. (1996) [Pubmed]
  23. Analysis of myelin proteolipid protein and F0 ATPase subunit 9 in normal and jimpy CNS. Benjamins, J.A., Studzinski, D.M., Skoff, R.P. Neurochem. Res. (1994) [Pubmed]
  24. Expression of myelin basic protein genes in several dysmyelinating mouse mutants during early postnatal brain development. Roth, H.J., Hunkeler, M.J., Campagnoni, A.T. J. Neurochem. (1985) [Pubmed]
  25. Posttranscriptional regulation of myelin protein gene expression. Campagnoni, A.T., Verdi, J.M., Verity, A.N., Amur-Umarjee, S., Byravan, S. Ann. N. Y. Acad. Sci. (1991) [Pubmed]
  26. An immortalized jimpy oligodendrocyte cell line: defects in cell cycle and cAMP pathway. Feutz, A.C., Pham-Dinh, D., Allinquant, B., Miehe, M., Ghandour, M.S. Glia (2001) [Pubmed]
  27. Developmental expression of glial fibrillary acidic protein and glutamine synthetase mRNAs in normal and jimpy mice. Li, X.S., Bartlett, W.P. Brain Res. Mol. Brain Res. (1991) [Pubmed]
  28. Survival of, and competition between, oligodendrocytes expressing different alleles of the Plp gene. Edgar, J.M., Anderson, T.J., Dickinson, P.J., Barrie, J.A., McCulloch, M.C., Nave, K.A., Griffiths, I.R. J. Cell Biol. (2002) [Pubmed]
  29. A predictable sequential determinant spreading cascade invariably accompanies progression of experimental autoimmune encephalomyelitis: a basis for peptide-specific therapy after onset of clinical disease. Yu, M., Johnson, J.M., Tuohy, V.K. J. Exp. Med. (1996) [Pubmed]
  30. A novel X gene with a widely transcribed Y-linked homologue escapes X-inactivation in mouse and human. Agulnik, A.I., Mitchell, M.J., Mattei, M.G., Borsani, G., Avner, P.A., Lerner, J.L., Bishop, C.E. Hum. Mol. Genet. (1994) [Pubmed]
  31. Disrupted compaction of CNS myelin in an OSP/Claudin-11 and PLP/DM20 double knockout mouse. Chow, E., Mottahedeh, J., Prins, M., Ridder, W., Nusinowitz, S., Bronstein, J.M. Mol. Cell. Neurosci. (2005) [Pubmed]
  32. Jimpy mice: quantitation of myelin-associated glycoprotein and other proteins. Yanagisawa, K., Quarles, R.H. J. Neurochem. (1986) [Pubmed]
  33. Developmental expression of the myelin proteolipid protein and basic protein mRNAs in normal and dysmyelinating mutant mice. Sorg, B.A., Smith, M.M., Campagnoni, A.T. J. Neurochem. (1987) [Pubmed]
  34. Expression of myelin protein genes and other myelin components in an oligodendrocytic cell line conditionally immortalized with a temperature-sensitive retrovirus. Verity, A.N., Bredesen, D., Vonderscher, C., Handley, V.W., Campagnoni, A.T. J. Neurochem. (1993) [Pubmed]
  35. Immunohistochemical studies on cross-transplantations between jimpy, shiverer, and normal newborn mice. Lachapelle, F., Lapie, P., Nussbaum, J.L., Gumpel, M. J. Neurosci. Res. (1990) [Pubmed]
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