Myelin mutants: New models and new observations

Lunn, Katharine F.; Fanarraga, Mónica L.; Duncan, Ian D.

doi:10.1002/jemt.1070320303

Cited by 39 publications

(29 citation statements)

References 102 publications

(143 reference statements)

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“…Ultrastructural observations on myelin mutants show that in the CNS, the integral proteolipid protein (PLP) may be involved with intermembrane interactions at the extracellular surfaces and that MBP is responsible for interactions at the cytoplasmic surfaces (or major dense line; reviewed by Lunn et al, 1995;Griffiths, 1996). Most of the studies carried out with MBP demonstrate its ability to bind to specific lipids and detergents (see above).…”

Section: Lipid-bound Mbp Promotes/stabilizes Formation Of Myelin-likementioning

confidence: 95%

Multilamellar packing of myelin modeled by lipid-bound MBP

Riccio¹,

Fasano²,

Borenshtein³

et al. 2000

J. Neurosci. Res.

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Membrane compaction and adhesion at the major dense line (cytoplasmic apposition) of myelin, particularly in the central nervous system (CNS), is typically attributed to myelin basic protein (MBP). To explore the role of MBP in myelin membrane adhesion, we attempted to reconstitute the major dense line of myelin from purified lipid-bound MBP, which is a detergent-soluble form of MBP that retains the binding of all the myelin lipids. Removal of detergent by long-term dialysis yielded a precipitate, which, when analyzed by sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) and thin-layer chromatography, contained MBP that was still associated with myelin lipids, but in different proportions than in the native membrane. Comparison of lipid composition among isolated myelin, MBP-free myelin lipids, and lipid-bound MBP aggregates showed that the lipid-bound form of the protein was specifically enriched in phosphatidylethanolamine, phosphatidylcholine, sphingomyelin, phosphatidylinositol, and phosphatidylserine. Electron microscopy and x-ray diffraction demonstrated that the lipid-MBP complexes formed multilayers having periods of 70-85 A, which correspond in width to individual myelin membranes. By contrast, the lipids alone assembled as multilayers having a period of approximately 40 A. Thus, the detergent-soluble form of MBP, which is bound to lipids, might serve as a simple model for the cytoplasmic apposition of myelin.

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Section: Lipid-bound Mbp Promotes/stabilizes Formation Of Myelin-likementioning

confidence: 95%

Multilamellar packing of myelin modeled by lipid-bound MBP

Riccio¹,

Fasano²,

Borenshtein³

et al. 2000

J. Neurosci. Res.

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“…Olig1-null mice develop severe neurological abnormalities, such as abnormal limb clasping, generalized tremors, ataxia, and tonic seizures (Fig. 1C), which are characteristic features of myelindeficient animals in which oligodendrocyte differentiation occurs normally but the synthesis of myelin sheaths is disrupted to varying degrees (Nave, 1994;Lunn et al, 1995;Gow et al, 1998).…”

Section: Olig1-null Mice Exhibit Severe Neurological Abnormalitiesmentioning

confidence: 99%

Myelinogenesis and Axonal Recognition by Oligodendrocytes in Brain Are Uncoupled inOlig1-Null Mice

Xin

Tao²,

et al. 2005

J. Neurosci.

238

254

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Myelin-forming oligodendrocytes facilitate saltatory nerve conduction and support neuronal functions in the mammalian CNS. Although the processes of oligodendrogliogenesis and differentiation from neural progenitor cells have come to light in recent years, the molecular mechanisms underlying oligodendrocyte myelinogenesis are poorly defined. Herein, we demonstrate the pivotal role of the basic helixloop-helix transcription factor, Olig1, in oligodendrocyte myelinogenesis in brain development. Mice lacking a functional Olig1 gene develop severe neurological deficits and die in the third postnatal week. In the brains of these mice, expression of myelin-specific genes is abolished, whereas the formation of oligodendrocyte progenitors is not affected. Furthermore, multilamellar wrapping of myelin membranes around axons does not occur, despite recognition and contact of axons by oligodendrocytes, and Olig1-null mice develop widespread progressive axonal degeneration and gliosis. In contrast, myelin sheaths are formed in the spinal cord, although the extent of myelination is severely reduced. At the molecular level, we find that Olig1 regulates transcription of the major myelin-specific genes, Mbp, Plp1, and Mag, and suppresses expression of a major astrocyte-specific gene, Gfap. Together, our data indicate that Olig1 is a central regulator of oligodendrocyte myelinogenesis in brain and that axonal recognition and myelination by oligodendrocytes are separable processes.

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“…The myelin disorder that characterizes this mutant is probably due to a defect in oligodendrocytes [Duncan et al, 1992;Lunn et al, 1995;Couve et al, 1997], leading to a disruption in the development and maintenance of central, but not peripheral, myelin. Cross-breeding experiments indicate that taiep rats are affected by an autosomal recessive mutation [Holmgren et al, 1989].…”

Section: Introductionmentioning

confidence: 99%

Progressive Deterioration of Central Components of Auditory Brainstem Responses during Postnatal Development of the Myelin Mutant <i>taiep</i> Rat

Roncagliolo

Benítez²,

Eguíbar³

2000

Audiol Neurotol

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Auditory brainstem responses (ABRs) were evaluated during the postnatal development (P10–P180) of taiep rats, neurological mutants characterized by early abnormal myelin development and subsequent demyelination of the CNS. The disorder is produced by an autosomal recessive mutation trait that affects the oligodendrocytes but not the Schwann cells. After onset of ABRs (P12–P14), taiep rats and their nonaffected heterozygous littermates that served as controls showed a similar pattern of maturation for wave I. The central waves (In–IV) showed significantly longer latencies in the mutants. By P60–P180, the later waves (III and IV) were frequently difficult to discern. From the onset of ABRs, the interpeak latency I–IV, corresponding to the central conduction time (CCT) of the auditory pathway, showed in taiep rats significantly longer values than controls. After an initial reduction, proportional to that of control rats, the CCT value increased progressively during the second month of the mutants’ lives. The electrophysiological results of the present study strongly support the hypothesis that mutation in the taiep rat impairs neuromaturation of the central auditory pathway in the brainstem by affecting the myelination process in the CNS.

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Myelin mutants: New models and new observations

Cited by 39 publications

References 102 publications

Multilamellar packing of myelin modeled by lipid-bound MBP

Multilamellar packing of myelin modeled by lipid-bound MBP

Myelinogenesis and Axonal Recognition by Oligodendrocytes in Brain Are Uncoupled inOlig1-Null Mice

Progressive Deterioration of Central Components of Auditory Brainstem Responses during Postnatal Development of the Myelin Mutant <i>taiep</i> Rat

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