Targeted expression of baculovirus p35 caspase inhibitor in oligodendrocytes protects mice against autoimmune-mediated demyelination

Shin Hisahara, Takashi Araki, Fumihiro Sugiyama, Ken Ichi Yagami, Misao Suzuki, Kuniya Abe, Ken Ichi Yamamura, Jun Ichi Miyazaki, Takashi Momoi, Takao Saruta, Claude C.A. Bernard, Hideyuki Okano, Masayuki Miura

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Abstract

The mechanisms underlying oligodendrocyte (OLG) loss and the precise roles played by OLG death in human demyelinating diseases such as multiple sclerosis (MS), and in the rodent model of MS, experimental autoimmune encephalomyelitis (EAE), remain to be elucidated. To clarify the involvement of OLG death in EAE, we have generated transgenic mice that express the baculovirus anti-apoptotic protein p35 in OLGs through the Cre-loxP system. OLGs from cre/p35 transgenic mice were resistant to tumor necrosis factor-α-, anti-Fas antibody- and interferon-γ-induced cell death. cre/p35 transgenic mice were resistant to EAE induction by immunization with the myelin oligodendrocyte glycoprotein. The numbers of infiltrating T cells and macrophages/microglia in the EAE lesions were significantly reduced, as were the numbers of apoptotic OLGs expressing the activated form of caspase-3. Thus, inhibition of apoptosis in OLGs by p35 expression alleviated the severity of the neurological manifestations observed in autoimmune demyelinating diseases.

Original languageEnglish
Pages (from-to)341-348
Number of pages8
JournalEMBO Journal
Volume19
Issue number3
Publication statusPublished - 2000 Feb 1

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Keywords

  • Apoptosis
  • Baculovirus p35
  • Caspase
  • Demyelination
  • Oligodendrocyte

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Hisahara, S., Araki, T., Sugiyama, F., Yagami, K. I., Suzuki, M., Abe, K., Yamamura, K. I., Miyazaki, J. I., Momoi, T., Saruta, T., Bernard, C. C. A., Okano, H., & Miura, M. (2000). Targeted expression of baculovirus p35 caspase inhibitor in oligodendrocytes protects mice against autoimmune-mediated demyelination. EMBO Journal, 19(3), 341-348.