CNS gene expression pattern associated with spontaneous experimental autoimmune encephalomyelitis

Agata Matejuk, Corwyn Hopke, Jami Dwyer, Sandhya Subramanian, Richard E. Jones, Dennis Bourdette, Arthur Vandenbark, Halina Offner

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Transgenic mice with T-cell receptor (TCR) specific for myelin basic protein (MBP)-Ac1-11 peptide and homozygous for the RAG-1 mutation (T/R- mice) spontaneously develop acute progressive experimental autoimmune encephalomyelitis (Sp-EAE) mediated by CD4+ T cells. Microarray analysis of spinal cord tissue obtained from symptomatic versus non-symptomatic T/R- mice revealed strongly upregulated transcripts for genes involved in antigen presentation and processing, signal transduction, transcription regulation, metabolism, development, cell cycle, and many other processes involved in the induction of clinical and pathological signs of Sp-EAE. Several highly expressed genes were related directly to inflammation, including cytokines/receptors, chemokines/receptors, acute phase, complement molecules, and others. Many CNS-specific genes were also upregulated in sick mice. Abundance of message for the Tg TCR BV8S2 gene as well as several monocyte/macrophage-associated genes would suggest that both components play a crucial role in the pathogenesis of Sp-EAE. The profile of transcriptional changes found during the development of Sp-EAE provides the first description of the encephalitogenic process in the absence of purposeful immunization with myelin peptides and immune-enhancing adjuvants. This unique approach is the first to implicate molecules and pathways that contribute naturally to onset of paralysis and demyelination, and thus may provide unique insights and novel treatment strategies for human diseases such as multiple sclerosis.

Original languageEnglish (US)
Pages (from-to)667-678
Number of pages12
JournalJournal of Neuroscience Research
Volume73
Issue number5
DOIs
StatePublished - Sep 1 2003

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Autoimmune Experimental Encephalomyelitis
Gene Expression
Antigen Presentation
Genes
T-Cell Receptor Genes
Peptides
Cytokine Receptors
Chemokine Receptors
Demyelinating Diseases
Microarray Analysis
Myelin Sheath
T-Cell Antigen Receptor
Paralysis
Transgenic Mice
Multiple Sclerosis
Monocytes
Immunization
Signal Transduction
Spinal Cord
Cell Cycle

Keywords

  • Microarray
  • Spinal cord
  • Spontaneous EAE

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

CNS gene expression pattern associated with spontaneous experimental autoimmune encephalomyelitis. / Matejuk, Agata; Hopke, Corwyn; Dwyer, Jami; Subramanian, Sandhya; Jones, Richard E.; Bourdette, Dennis; Vandenbark, Arthur; Offner, Halina.

In: Journal of Neuroscience Research, Vol. 73, No. 5, 01.09.2003, p. 667-678.

Research output: Contribution to journalArticle

Matejuk, Agata ; Hopke, Corwyn ; Dwyer, Jami ; Subramanian, Sandhya ; Jones, Richard E. ; Bourdette, Dennis ; Vandenbark, Arthur ; Offner, Halina. / CNS gene expression pattern associated with spontaneous experimental autoimmune encephalomyelitis. In: Journal of Neuroscience Research. 2003 ; Vol. 73, No. 5. pp. 667-678.
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