Absence of MHC class ii molecules reduces CNS demyelination, microglial/macrophage infiltration, and twitching in murine globoid cell leukodystrophy

Glenn K. Matsushima, Masako Taniike, Laurie H. Glimcher, Michael J. Grusby, Jeffrey A Frelinger, Kinuko Suzuki, Jenny P Y Ting

Research output: Contribution to journalArticle

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Abstract

Globoid cell leukodystrophy (GILD) is a severe genetic demyelinating disorder with an increased number of la (immune response antigen) positive brain microglia/ macrophages. To assess the role of aberrant la expression in the central nervous system (CNS), twitcher mice, which represent the murine model for GLD, were mated with la-- transgenic mice. Compared with the la+ controls, la- twitcher mice showed a profound reduction in the severity of demyelinating lesions correlated with significantly fewer microglia/macrophages. Most importantly, la- twitcher mice showed significantly reduced twitching compared with la+ twitcher mice. In contrast with experimental allergic encephalomyelitis (EAE), there was no significant amount of Inflammatory T cell infiltrates, implying that T cells may not play a predominant role In this disease. These findings may have broad therapeutic implications for Alzheimer's disease, Parkinson's disease, and Huntington's disease, which display enhanced la expression in the CNS without obvious T cell Infiltrates.

Original languageEnglish (US)
Pages (from-to)645-656
Number of pages12
JournalCell
Volume78
Issue number4
DOIs
StatePublished - Aug 26 1994
Externally publishedYes

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Globoid Cell Leukodystrophy
Macrophages
Neurology
Demyelinating Diseases
Infiltration
T-cells
Central Nervous System
Molecules
Microglia
T-Lymphocytes
Inborn Genetic Diseases
Autoimmune Experimental Encephalomyelitis
Histocompatibility Antigens Class II
Huntington Disease
Transgenic Mice
Parkinson Disease
Brain
Alzheimer Disease

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Absence of MHC class ii molecules reduces CNS demyelination, microglial/macrophage infiltration, and twitching in murine globoid cell leukodystrophy. / Matsushima, Glenn K.; Taniike, Masako; Glimcher, Laurie H.; Grusby, Michael J.; Frelinger, Jeffrey A; Suzuki, Kinuko; Ting, Jenny P Y.

In: Cell, Vol. 78, No. 4, 26.08.1994, p. 645-656.

Research output: Contribution to journalArticle

Matsushima, Glenn K. ; Taniike, Masako ; Glimcher, Laurie H. ; Grusby, Michael J. ; Frelinger, Jeffrey A ; Suzuki, Kinuko ; Ting, Jenny P Y. / Absence of MHC class ii molecules reduces CNS demyelination, microglial/macrophage infiltration, and twitching in murine globoid cell leukodystrophy. In: Cell. 1994 ; Vol. 78, No. 4. pp. 645-656.
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abstract = "Globoid cell leukodystrophy (GILD) is a severe genetic demyelinating disorder with an increased number of la (immune response antigen) positive brain microglia/ macrophages. To assess the role of aberrant la expression in the central nervous system (CNS), twitcher mice, which represent the murine model for GLD, were mated with la-- transgenic mice. Compared with the la+ controls, la- twitcher mice showed a profound reduction in the severity of demyelinating lesions correlated with significantly fewer microglia/macrophages. Most importantly, la- twitcher mice showed significantly reduced twitching compared with la+ twitcher mice. In contrast with experimental allergic encephalomyelitis (EAE), there was no significant amount of Inflammatory T cell infiltrates, implying that T cells may not play a predominant role In this disease. These findings may have broad therapeutic implications for Alzheimer's disease, Parkinson's disease, and Huntington's disease, which display enhanced la expression in the CNS without obvious T cell Infiltrates.",
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