The early phenotype associated with the jimpy mutation of the proteolipid protein gene

C. E. Thomson, T. J. Anderson, M. C. McCulloch, Peter J Dickinson, D. A. Vouyiouklis, I. R. Griffiths

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The jimpy mutation of the X-linked proteolipid protein (Plp) gene causes dysmyelination and premature death of the mice. The established phenotype is characterised by severe hypomyelination, increased numbers of dead oligodendrocytes and astrocytosis. The purpose of this study was to define the earliest cellular abnormalities in the cervical spinal cord. We find that on the first and third postnatal days the amount of myelin in jimpy spinal cord is approximately 20% of wild-type. However, the total glial cell density, the number of dead glial cells and the number and distribution of Plp-positive cells, as assessed by in situ hybridization, are similar to wild-type during the first week of life. Immunostaining of cryosections has identified that jimpy spinal cords express on schedule, a variety of antigens associated with mature oligodendrocytes. Dissociated oligodendrocytes, cultured for 18 hours to reflect their in vivo differentiation, express MBP and surface myelin-associated glycoprotein at the same frequency as wild- type. By comparison, the proportion of jimpy oligodendrocytes expressing surface myelin/oligodendrocyte glycoprotein is reduced by approximately 34%. In vivo, however, only a small minority of axons is surrounded by a collar of myelin-associated glycoprotein, suggesting that the majority of jimpy oligodendrocytes fail to make appropriate ensheathment of axons. Although the DM20 isoform is expressed in the embryonic CNS prior to myelin formation, the cellular abnormalities appear to correspond to the time at which the Plp isoform becomes predominant. The results suggest that the primary abnormality in jimpy is the inability of oligodendrocytes to properly associate with, and then ensheath, axons and that oligodendrocyte death compounds, rather than initiates, the established phenotype.

Original languageEnglish (US)
Pages (from-to)207-221
Number of pages15
JournalJournal of Neurocytology
Volume28
Issue number3
DOIs
StatePublished - 1999
Externally publishedYes

Fingerprint

Proteolipids
Oligodendroglia
Phenotype
Mutation
Myelin-Associated Glycoprotein
Proteins
Axons
Cell Count
Membrane Glycoproteins
Myelin Sheath
Neuroglia
Spinal Cord
Protein Isoforms
Myelin-Oligodendrocyte Glycoprotein
Premature Mortality
Gliosis
In Situ Hybridization
Cause of Death
Appointments and Schedules
Antigens

ASJC Scopus subject areas

  • Neuroscience(all)
  • Anatomy
  • Cell Biology
  • Histology

Cite this

Thomson, C. E., Anderson, T. J., McCulloch, M. C., Dickinson, P. J., Vouyiouklis, D. A., & Griffiths, I. R. (1999). The early phenotype associated with the jimpy mutation of the proteolipid protein gene. Journal of Neurocytology, 28(3), 207-221. https://doi.org/10.1023/A:1007024022663

The early phenotype associated with the jimpy mutation of the proteolipid protein gene. / Thomson, C. E.; Anderson, T. J.; McCulloch, M. C.; Dickinson, Peter J; Vouyiouklis, D. A.; Griffiths, I. R.

In: Journal of Neurocytology, Vol. 28, No. 3, 1999, p. 207-221.

Research output: Contribution to journalArticle

Thomson, CE, Anderson, TJ, McCulloch, MC, Dickinson, PJ, Vouyiouklis, DA & Griffiths, IR 1999, 'The early phenotype associated with the jimpy mutation of the proteolipid protein gene', Journal of Neurocytology, vol. 28, no. 3, pp. 207-221. https://doi.org/10.1023/A:1007024022663
Thomson, C. E. ; Anderson, T. J. ; McCulloch, M. C. ; Dickinson, Peter J ; Vouyiouklis, D. A. ; Griffiths, I. R. / The early phenotype associated with the jimpy mutation of the proteolipid protein gene. In: Journal of Neurocytology. 1999 ; Vol. 28, No. 3. pp. 207-221.
@article{559cb10093cf4a19b80d2531abb53467,
title = "The early phenotype associated with the jimpy mutation of the proteolipid protein gene",
abstract = "The jimpy mutation of the X-linked proteolipid protein (Plp) gene causes dysmyelination and premature death of the mice. The established phenotype is characterised by severe hypomyelination, increased numbers of dead oligodendrocytes and astrocytosis. The purpose of this study was to define the earliest cellular abnormalities in the cervical spinal cord. We find that on the first and third postnatal days the amount of myelin in jimpy spinal cord is approximately 20{\%} of wild-type. However, the total glial cell density, the number of dead glial cells and the number and distribution of Plp-positive cells, as assessed by in situ hybridization, are similar to wild-type during the first week of life. Immunostaining of cryosections has identified that jimpy spinal cords express on schedule, a variety of antigens associated with mature oligodendrocytes. Dissociated oligodendrocytes, cultured for 18 hours to reflect their in vivo differentiation, express MBP and surface myelin-associated glycoprotein at the same frequency as wild- type. By comparison, the proportion of jimpy oligodendrocytes expressing surface myelin/oligodendrocyte glycoprotein is reduced by approximately 34{\%}. In vivo, however, only a small minority of axons is surrounded by a collar of myelin-associated glycoprotein, suggesting that the majority of jimpy oligodendrocytes fail to make appropriate ensheathment of axons. Although the DM20 isoform is expressed in the embryonic CNS prior to myelin formation, the cellular abnormalities appear to correspond to the time at which the Plp isoform becomes predominant. The results suggest that the primary abnormality in jimpy is the inability of oligodendrocytes to properly associate with, and then ensheath, axons and that oligodendrocyte death compounds, rather than initiates, the established phenotype.",
author = "Thomson, {C. E.} and Anderson, {T. J.} and McCulloch, {M. C.} and Dickinson, {Peter J} and Vouyiouklis, {D. A.} and Griffiths, {I. R.}",
year = "1999",
doi = "10.1023/A:1007024022663",
language = "English (US)",
volume = "28",
pages = "207--221",
journal = "Journal of Neurocytology",
issn = "0300-4864",
publisher = "Kluwer Academic Publishers",
number = "3",

}

TY - JOUR

T1 - The early phenotype associated with the jimpy mutation of the proteolipid protein gene

AU - Thomson, C. E.

AU - Anderson, T. J.

AU - McCulloch, M. C.

AU - Dickinson, Peter J

AU - Vouyiouklis, D. A.

AU - Griffiths, I. R.

PY - 1999

Y1 - 1999

N2 - The jimpy mutation of the X-linked proteolipid protein (Plp) gene causes dysmyelination and premature death of the mice. The established phenotype is characterised by severe hypomyelination, increased numbers of dead oligodendrocytes and astrocytosis. The purpose of this study was to define the earliest cellular abnormalities in the cervical spinal cord. We find that on the first and third postnatal days the amount of myelin in jimpy spinal cord is approximately 20% of wild-type. However, the total glial cell density, the number of dead glial cells and the number and distribution of Plp-positive cells, as assessed by in situ hybridization, are similar to wild-type during the first week of life. Immunostaining of cryosections has identified that jimpy spinal cords express on schedule, a variety of antigens associated with mature oligodendrocytes. Dissociated oligodendrocytes, cultured for 18 hours to reflect their in vivo differentiation, express MBP and surface myelin-associated glycoprotein at the same frequency as wild- type. By comparison, the proportion of jimpy oligodendrocytes expressing surface myelin/oligodendrocyte glycoprotein is reduced by approximately 34%. In vivo, however, only a small minority of axons is surrounded by a collar of myelin-associated glycoprotein, suggesting that the majority of jimpy oligodendrocytes fail to make appropriate ensheathment of axons. Although the DM20 isoform is expressed in the embryonic CNS prior to myelin formation, the cellular abnormalities appear to correspond to the time at which the Plp isoform becomes predominant. The results suggest that the primary abnormality in jimpy is the inability of oligodendrocytes to properly associate with, and then ensheath, axons and that oligodendrocyte death compounds, rather than initiates, the established phenotype.

AB - The jimpy mutation of the X-linked proteolipid protein (Plp) gene causes dysmyelination and premature death of the mice. The established phenotype is characterised by severe hypomyelination, increased numbers of dead oligodendrocytes and astrocytosis. The purpose of this study was to define the earliest cellular abnormalities in the cervical spinal cord. We find that on the first and third postnatal days the amount of myelin in jimpy spinal cord is approximately 20% of wild-type. However, the total glial cell density, the number of dead glial cells and the number and distribution of Plp-positive cells, as assessed by in situ hybridization, are similar to wild-type during the first week of life. Immunostaining of cryosections has identified that jimpy spinal cords express on schedule, a variety of antigens associated with mature oligodendrocytes. Dissociated oligodendrocytes, cultured for 18 hours to reflect their in vivo differentiation, express MBP and surface myelin-associated glycoprotein at the same frequency as wild- type. By comparison, the proportion of jimpy oligodendrocytes expressing surface myelin/oligodendrocyte glycoprotein is reduced by approximately 34%. In vivo, however, only a small minority of axons is surrounded by a collar of myelin-associated glycoprotein, suggesting that the majority of jimpy oligodendrocytes fail to make appropriate ensheathment of axons. Although the DM20 isoform is expressed in the embryonic CNS prior to myelin formation, the cellular abnormalities appear to correspond to the time at which the Plp isoform becomes predominant. The results suggest that the primary abnormality in jimpy is the inability of oligodendrocytes to properly associate with, and then ensheath, axons and that oligodendrocyte death compounds, rather than initiates, the established phenotype.

UR - http://www.scopus.com/inward/record.url?scp=0033499833&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033499833&partnerID=8YFLogxK

U2 - 10.1023/A:1007024022663

DO - 10.1023/A:1007024022663

M3 - Article

VL - 28

SP - 207

EP - 221

JO - Journal of Neurocytology

JF - Journal of Neurocytology

SN - 0300-4864

IS - 3

ER -