Dysmyelination in transgenic mice resulting from expression of class I histocompatibility molecules in oligodendrocytes

Ann M. Turnley, Grant Morahan, Hideyuki Okano, Ora Bernard, Katsuhiko Mikoshiba, Janette Allison, Perry F. Bartlett, J. F A P Miller

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Abstract

MAJOR histocompatibility complex (MHC) molecules are not normally expressed in the central nervous system (CNS)1-3. However, aberrant expression has been observed in multiple sclerosis lesions and could contribute to the destruction of myelin or the myelinating cells known as oligodendrocytes4,5. The mechanism of cell damage associated with aberrant MHC molecule expression is unclear: for example, overexpression of class I (ref. 6) and class II (refs 7, 8) MHC molecules in pancreatic β cells in transgenic mice leads to nonimmune destruction of the cells and insulin-dependent diabetes mellitus. We have generated transgenic mice that express class I H-2Kb MHC molecules, under the control of the myelin basic protein promoter, specifically in oligodendrocytes. Homozygous transgenic mice have a shivering phenotype, develop tonic seizures and die at 15-22 days. This phenotype, which we term 'wonky', is due to hypomyelination in the CNS, and not to involvement of the immune system. The primary defect appears to be a shortage of myelinating oligodendrocytes resulting from overexpression of the class I MHC molecules.

Original languageEnglish
Pages (from-to)566-569
Number of pages4
JournalNature
Volume353
Issue number6344
Publication statusPublished - 1991 Oct 10
Externally publishedYes

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Histocompatibility
Oligodendroglia
Major Histocompatibility Complex
Transgenic Mice
Central Nervous System
Shivering
Phenotype
Myelin Basic Protein
Myelin Sheath
Type 1 Diabetes Mellitus
Multiple Sclerosis
Immune System
Seizures

ASJC Scopus subject areas

  • General

Cite this

Turnley, A. M., Morahan, G., Okano, H., Bernard, O., Mikoshiba, K., Allison, J., ... Miller, J. F. A. P. (1991). Dysmyelination in transgenic mice resulting from expression of class I histocompatibility molecules in oligodendrocytes. Nature, 353(6344), 566-569.

Dysmyelination in transgenic mice resulting from expression of class I histocompatibility molecules in oligodendrocytes. / Turnley, Ann M.; Morahan, Grant; Okano, Hideyuki; Bernard, Ora; Mikoshiba, Katsuhiko; Allison, Janette; Bartlett, Perry F.; Miller, J. F A P.

In: Nature, Vol. 353, No. 6344, 10.10.1991, p. 566-569.

Research output: Contribution to journalArticle

Turnley, AM, Morahan, G, Okano, H, Bernard, O, Mikoshiba, K, Allison, J, Bartlett, PF & Miller, JFAP 1991, 'Dysmyelination in transgenic mice resulting from expression of class I histocompatibility molecules in oligodendrocytes', Nature, vol. 353, no. 6344, pp. 566-569.
Turnley AM, Morahan G, Okano H, Bernard O, Mikoshiba K, Allison J et al. Dysmyelination in transgenic mice resulting from expression of class I histocompatibility molecules in oligodendrocytes. Nature. 1991 Oct 10;353(6344):566-569.
Turnley, Ann M. ; Morahan, Grant ; Okano, Hideyuki ; Bernard, Ora ; Mikoshiba, Katsuhiko ; Allison, Janette ; Bartlett, Perry F. ; Miller, J. F A P. / Dysmyelination in transgenic mice resulting from expression of class I histocompatibility molecules in oligodendrocytes. In: Nature. 1991 ; Vol. 353, No. 6344. pp. 566-569.
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