Skip to main content
SpringerLink
Log in

Myelin protein expression in the myelin-deficient rat brain and cultured oligodendrocytes

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

The myelin-deficient (MD) rat does not express the major protein of CNS myelin, proteolipid protein (PLP). Here we further analyze whether this defect is reflected at the level of mRNA and whether the expression of other myelin proteins is affected in oligodendrocytes in vivo and in vitro. Both myelin basic protein (MBP) and PLP message levels were reduced in MD rats to 10–20% of the normal littermate controls, while the level of expression of an astrocyte-specific gene, glial fibrillary acidic protein (GFAP), was normal. Although MBP and PLP mRNAs were equally depressed, only MBP was detected with immunolabeling of corpus callosum, while PLP was absent in oligodendrocytes both in vivo and in vitro. A reduced number of MD rat oligodendrocytes express MBP in vitro compared to controls. The MD rat optic nerve contains normal numbers of 0–2A progenitors, but they tend to differentiate into GC-positive oligodendrocytes faster than oligodendrocytes from control littermates. In conclusion, the absence of PLP and reduced levels of MBP in the MD rats point to similarities with the jimpy mouse lesion. Moreover, the defect influences the expression of other myelin proteins and the oligodendrocyte developmental pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abney, E.R., Barlett, D.P., Raff, M.C. (1981). Astrocytes, ependymal cells, and oligodendrocytes develop on schedule in dissociated cell cultures of embryonic rat brain. Dev. Biol. 83:301–310

    Article  PubMed  CAS  Google Scholar 

  • Avia, H., Leder, P. (1972). Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc. Natl. Acad. Sci. U.S.A. 69:1408–1412

    Article  Google Scholar 

  • Barbarese, E., Nielson, M.L., Carson J.H. (1983). The effect of the shiverer mutation on myelin basic protein expression in homozygous and heterzygous mouse brain. J. Neurochem. 40:1680–1686

    Article  PubMed  CAS  Google Scholar 

  • Bauman, N. (1980). Neurological Mutations Affecting Myelination. INSERM Symposium, No. 14, Elsevier/North Holland, Amsterdam, 565 pages

    Google Scholar 

  • Bologa-Sandru, L., Zalc, B., Herschkowitz, N., Baumann, N. (1981). Oligodendrocytes of jimpy mice express galactosylceramide: an immunofluorescence study on brain sections and dissociated brain cell cultures. Brain Res. 225:425–430

    Article  PubMed  CAS  Google Scholar 

  • Campagnoni, C.W., Carey, G.D., Campagnoni, A.J. (1978). Synthesis of myelin basic proteins in the developing mouse brain. Arch. Biochem. Biophys. 190: 118–125

    Article  PubMed  CAS  Google Scholar 

  • Carson, J.H., Nielson, M.L., Barbarese, E. (1983). Developmental regulation of myelin basic protein expression in mouse brain. Dev. Biol. 96:485–492

    Article  PubMed  CAS  Google Scholar 

  • Cohen, S.R., Guarnieri, M. (1976). Immunochemical measurement of myelin basic protein in developing rat brain: an index of myelin synthesis. Dev. Biol. 49:294–299

    Article  PubMed  CAS  Google Scholar 

  • Csiza, C.K. (1982). Lipid class analysis of the central nervous system of myelin deficient Wistar rats. J. Lipid Res. 23:720–725

    PubMed  CAS  Google Scholar 

  • Csiza, C.K., deLabunta, A. (1979). Myelin deficiency (md): A neurologic mutant in the Wistar rat. Am. J. Pathol. 95:215–224

    PubMed  CAS  Google Scholar 

  • de Ferra, F., Engh, H., Hudson, L., Kamholz, J., Puckett, C., Molineaux, S., Lazzarini, R.A. (1985): Alternative splicing accounts for the four forms of myelin basic protein. Cell 43:721–727

    Article  PubMed  Google Scholar 

  • Dentinger, M.P., Barron, K.D., Csiza, C.K. (1982). Ultrastructure of the central nervous system in a myelin deficient rat. J. Neurocytol. 11:671–691

    Article  PubMed  CAS  Google Scholar 

  • Dentinger, M.P., Barron, K.D., Csiza, C.K. (1985). Glial and axonal development in optic nerve of myelin deficient rat mutant. Brain Res. 344:255–266

    Article  PubMed  CAS  Google Scholar 

  • Dubois-Dalcq, M., Behar, T., Hudson, L., Lazzarini, R.A. (1986). Emergence of three myelin proteins in oligodendrocytes cultured without neurons. J. Cell. Biol. 102:384–393

    Article  PubMed  CAS  Google Scholar 

  • Duncan, I.D., Hammang, J.P., Jackson, K.F. (1987a). Jimpy myelin lacks PLP and has a defect in the intraperiod line. Soc. Neurosci. 13:118

    Google Scholar 

  • Duncan, I.D., Hammang, J.P., Trapp, B.D. (1987b): Abnormal compact myelin in the myelin deficient rat: Absence of proteolipid protein corresponds with a defect in the intraperiod line. Proc. Natl. Acad. Sci. U.S.A. 84:6287–6291

    Article  PubMed  CAS  Google Scholar 

  • Dupovey, P., Jacque, C., Bourre, J.M., Cesselin, F., Privat, A., Baumann, N. (1979). Immunochemical studies of myelin basic protein in shiverer mouse devoid of major dense line of myelin. Neurosci. Lett. 12:113–118

    Article  Google Scholar 

  • Eccelston, P.A., Silberberg, D.H. (1984). The differentiation of oligodendrocytes in a serum-free hormone-supplemented medium. Dev. Brain Res. 16:1–9

    Article  Google Scholar 

  • Eisenbarth, G.S., Walsh, F.S., Nirenberg, N. (1979). Monoclonal antibody to a plasma membrane antigen of neurons. Proc. Natl. Acad. Sci. U.S.A. 76:4913–4917

    Article  PubMed  CAS  Google Scholar 

  • Gardinier, M.V., Macklin, W.B., Diniak, A.J., Deininger, P.L. (1986). Characterization of myelin proteolipid mRNAs in normal and jimpy mice. Mol. Cell Biol. 6:3755–3762

    PubMed  CAS  Google Scholar 

  • Hartman, B.K., Agaral, H.C., Kalmbach, S., Shearer, W.T. (1979). A comparative study of the immunohistochemical localization of basic protein to myelin and oligodendrocytes in rat and chicken brain. J. Comp. Neurol. 188:273–290

    Article  PubMed  CAS  Google Scholar 

  • Hartman, B.K., Agrawal, H.C., Agrawal, D., Kalmbach, S. (1982). Development and maturation of central nervous system myelin: comparison of immunohistochemical localization of proteolipid protein and basic protein in myelin and oligodendrocytes. Proc. Natl. Acad. Sci. U.S.A. 79:4217–4220

    Article  PubMed  CAS  Google Scholar 

  • Hogan, E.L., Greenfield, S. (1984). Animal models of genetic disorders of myelin. In Myelin, P. Morell (ed) Plenum Press, New York, pp. 489–534

    Google Scholar 

  • Hudson, L.D., Berndt, J.A., Puckett, C., Kozak, C.A., Lazzarini, R.A. (1987). Aberrant splicing of proteolipid protein mRNA in the dysmyelinating jimpy mutant mouse. Proc. Natl. Acad. Sci. U.S.A. 84:1454–1458

    Article  PubMed  CAS  Google Scholar 

  • Jackson, F., Duncan, I.D. (1988). Cell kinetics and cell death in the optic nerve of the myelin deficient rat. J. Neurocytol (in press)

  • Joseph, K.C., Hogan, E.L. (1971). Fatty acid composition of cerebrosides, sulphatides, and ceramides in murine sudanophilic leucodystrophy. The jimpy mutant. J. Neurochem. 18:1639–1645

    Article  PubMed  CAS  Google Scholar 

  • Kamholz, J., de Ferra, F., Puckett, C., Lazzarini, R.A. (1986). Identification of three forms of human myelin basic protein by cDNA cloning. Proc. Natl. Acad. Sci. U.S.A. 83:4962–4966

    Article  PubMed  CAS  Google Scholar 

  • Kerner, A.L., Carson, J.H. (1984). Effect of the jimpy mutation on expression of myelin proteins in heterozygous and hemizygous mouse brain. J. Neurochem. 43:1706–1715

    Article  PubMed  CAS  Google Scholar 

  • Knapp, P.E., Skoff, R.P., Redstone, D.W. (1987). Oligodentroglial cell death in jimpy mice: An explanation for the myelin deficit. J. Neurosci. 10:2813–2822

    Google Scholar 

  • Kristensson, K., Zeller, N.K., Dubois-Dalcq, M., Lazzarini, R.A. (1986). Expression of myelin basic protein gene in the developing rat brain as revealed by in situ hybridization. J. Histochem. Cytochem. 34:467–473

    PubMed  CAS  Google Scholar 

  • Lewis, S.A., Balcarek, J.B., Krek, V., Shelaviki, M., Cowan, N.J. (1984). Sequence of a cDNA clone encoding mouse glial fibrillary acidic protein: Structural conservation of intermediate filaments. Proc. Natl. Acad. Sci. U.S.A. 81: 2743–2746

    Article  PubMed  CAS  Google Scholar 

  • Macklin, W.B., Gardinier, M.V., King, K.D., Kampf, K. (1987). An AG→GG transition at a splice site in the myelin proteolipid protein gene in jimpy mice results in the removal of an exon. FEBS Lett. 223:417–421

    Article  PubMed  CAS  Google Scholar 

  • Maniatis, T., Fritsch, E.F., Sambrook, J. (1982). Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Press, Cold Spring Harbor, NY

    Google Scholar 

  • McLean, I.W., Nakane, P.K. (1974). Periodate-lysine-paraformaldehyde fixative: A new fixative for immunoelectron microscope. J. Histochem. Cytochem. 22:1077–1083

    PubMed  CAS  Google Scholar 

  • Molineaux, S.M., Engh, H., de Ferra, F., Hudson, L., Lazzarini, R.A. (1986). Recombination within the myelin basic protein gene created the demyelinating shiverer mouse mutation. Proc. Natl. Acad. Sci. U.S.A. 83:7542–7546

    Article  PubMed  CAS  Google Scholar 

  • Morello, D., Dautigny, A., Pham-Dinh, D., Jolles, P. (1986). Myeiln proteolipid protein (PLP and DM-20) transcripts are deleted in jimpy mice. EMBO J. 5: 3489–3493

    PubMed  CAS  Google Scholar 

  • Nave, K.A., Lai, C., Bloom, F.E., Milner, R.J. (1986). Jimpy mutant mouse: A 74 base deletion in the mRNA for myelin proteolipid protein and evidence for a primary defect in RNA splicing. Proc. Natl. Acad. Sci. U.S.A. 83:9264–9268

    Article  PubMed  CAS  Google Scholar 

  • Nobel, M., Murray, K. (1984). Purified astrocytes promote the in vitro division of a bipotential glial progenitor cell. EMBO J. 3:2243–2247

    Google Scholar 

  • Norton, W.T., Poduslo, S.E. (1973). Myelimation in rat brain: Changes in myelin composition during brain maturation. J. Neurochem. 21:759–773

    Article  PubMed  CAS  Google Scholar 

  • Privat, A., Jacque, C., Bourre, J.M., Dupouey, P., Bauman, N. (1979). Absence of the major dense line in myelin of the mutant mouse “Shiverer”. Neurosci. Lett. 12:107–112

    Article  PubMed  CAS  Google Scholar 

  • Pruss, R.M. (1979). Thy-1 antigen on astrocytes in long term cultures of rat central nervous system. Nature 280:688–690

    Article  PubMed  CAS  Google Scholar 

  • Raff, M.D., Miller, R., Noble, M. (1983). A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on the culture medium. Nature 303:390–396

    Article  PubMed  CAS  Google Scholar 

  • Ranscht, B.P., Clapshaw, A., Price, J., Noble, M., Seifert, W. (1982). Development of oligodendrocytes and Schwann cells studied with a monoclonal antibody against galactocerebroside. Proc. Natl. Acad. Sci. U.S.A. 79:2709–2713

    Article  PubMed  CAS  Google Scholar 

  • Rigby, P.W.J., Dieckman, M., Rhodes, C., Berg, P. (1977). Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J. Mol. Biol. 113:237–251, 1984

    Article  PubMed  CAS  Google Scholar 

  • Roussel, G., Neskovic, N.M., Triffilieffi, E., Artault, J.-C., Nussbaum, J.L. (1987). Arrest of proteolipid transport through the Golgi apparatus in jimpy brain. J. Neurocytol. 16:195–204

    Article  PubMed  CAS  Google Scholar 

  • Sidman, R.L., Dickie, M.M., Appel, S.H. (1964). Mutant mice (quaking and jimpy) with deficient myelination in the central nervous system. Science 140:309–311

    Article  Google Scholar 

  • Sorg, B.J.A., Agrawal, A., Agrawal, H.C., Campagnoni, A.T. (1986). Expression of proteolipid protein and basic protein in normal and dysmyelinating mutant mice. J. Neurochem. 46:379–387

    Article  PubMed  CAS  Google Scholar 

  • Sternberger, N.H., Itoyama, Y., Kies, M.W., Webster, H.deF. (1978a). Myelin basic protein demonstrated immunocytochemically in oligodendroglia prior to myelin sheath formation. Proc. Natl. Acad. Sci. U.S.A. 75:2521–2524

    Article  PubMed  CAS  Google Scholar 

  • Sternberger, N.H., Itoyama, Y., Kies, M.W., Webster, H.deF. (1978b). Immunocytochemical method to identify basic protein in myelin-forming oligodendroctyes of newborn rat CNS. J. Neurocytol. 7:251–263

    Article  PubMed  CAS  Google Scholar 

  • Thomas, P. (1980). Hybridization of denatured RNA and DNA fragments transferred to nitrocellulose. Proc. Natl. Acad. Sci. U.S.A. 77:5201–5205

    Article  PubMed  CAS  Google Scholar 

  • Willard, H.F., Riordan, J.R. (1985). Assignment of the gene for myelin proteolipid protein to the X chromosome: Implications for X-linked myelin disorders. Science 230:940–942

    Article  PubMed  CAS  Google Scholar 

  • Yanagisawa, K., Quarles, R.H. (1986). Jimpy mice: Quantitation of myelin-associated glycoprotein and other proteins. J. Neurochem. 47:322–325

    Article  PubMed  CAS  Google Scholar 

  • Yanagisawa, K., Duncan, I.D., Hammang, J.P., Quaries, R.H. (1986). Myelin-deficient rat: Analysis of myelin proteins. J. Neurochem. 47:1901–1907

    Article  PubMed  CAS  Google Scholar 

  • Zalc, B., Mongen, M., Bauman, N. (1980). Immunohistochemical localization of galactosylceramide and sulfogalactosylceramide in the cerebellum of the quaking, shiverer, and jimpy mice. Neurological Mutations Affecting Myelination, INSERM Symposium No. 14. Elsevier/North Holland, Amsterdam, pp 263–268

    Google Scholar 

  • Zeller, N.K., Hunkeler, M.J., Campagnoni, A.T., Sprague, J., Lazzarini, R.A. (1984). Characterization of mouse myelin basic protein messenger RNAs with a myelin basic protein cDNA clone. Proc. Natl. Acad. Sci. U.S.A. 81:18–22

    Article  PubMed  CAS  Google Scholar 

  • Zeller, N.K., Behar, T.N., Dubois-Dalcq, M.F., Lazzarini, R.A. (1985). The timely expression of myelin basic protein gene in cultured rat brain oligodendrocytes is independent of continuous neuronal influences. J. Neurosci. 5:2955–2962

    PubMed  CAS  Google Scholar 

Download references

Author information

Author notes

  1. M. Dubois-Dalcq

    Present address: Laboratory of Viral and Molecular Pathogenesis, National Institute of Neurological Disorders and Stroke, NIH, Building 36, Room 5D04, Bethesda, MD, USA

  2. R. A. Lazzarini

    Present address: Brookdale Center for Molecular Biology, Mount Sinai Medical Center, One Gustave Levi Place, New York, NY, USA

Authors and Affiliations

  1. Laboratory of Molecular Genetics, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 36, Room 4A01, 20892, Bethesda, MD, USA

    N. K. Zeller, M. Dubois-Dalcq & R. A. Lazzarini

Authors
  1. N. K. Zeller
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Dubois-Dalcq
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. A. Lazzarini
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zeller, N.K., Dubois-Dalcq, M. & Lazzarini, R.A. Myelin protein expression in the myelin-deficient rat brain and cultured oligodendrocytes. J Mol Neurosci 1, 139–149 (1989). https://doi.org/10.1007/BF02918900

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02918900

Keywords

Search

Navigation