Genetically dominant spinal cord repair in a murine model of chronic progressive multiple sclerosis

Allan J. Bieber, Daren R. Ure, Moses Rodriguez

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

For reasons that are not well understood, central nervous system repair in multiple sclerosis is often minimal. We present evidence, in a murine model of chronic progressive multiple sclerosis, that genetic factors can substantially influence remyelination, axonal integrity, and neurologic function. Four inbred mouse strains, SJL, B10.D1-H2q, FVB, and SWR, developed extensive inflammatory demyelination by 3 months after infection with Theiler's murine encephalomyelitis virus. Demyelination continued lifelong in SJL and B10.D1-H2q mice, accompanied by axonal injury, minimal remyelination, and progressive motor dysfunction. In contrast, FVB and SWR mice showed less axonal injury, progressive remyelination, and stabilization of motor function. Genetic dominance of the reparative traits was demonstrated by crossing remyelinating strains (FVB and SWR) with nonremyelinating strains (SJL and B10.D1-H2q). All F1 mice developed a phenotype identical to FVB and SWR, showing extensive remyelination, partial preservation of axons, and preserved motor function. Analyses of viral RNA and antigen, immune cell infiltration, and antiviral antibody titers did not predict the phenotypic differences between strains. These results highlight the significant extent to which hereditary factors can control disease course and demonstrate that the switch from a pathogenic to a reparative phenotype can occur even after prolonged inflammatory demyelination.

Original languageEnglish (US)
Pages (from-to)46-57
Number of pages12
JournalJournal of Neuropathology and Experimental Neurology
Volume64
Issue number1
StatePublished - Jan 2005

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Spinal Cord Regeneration
Chronic Progressive Multiple Sclerosis
Demyelinating Diseases
Theilovirus
Phenotype
Inbred Strains Mice
Viral Antigens
Wounds and Injuries
Viral RNA
Nervous System
Multiple Sclerosis
Antiviral Agents
Axons
Central Nervous System
Antibodies
Infection

Keywords

  • CNS repair
  • Genetics
  • Multiple sclerosis
  • Remyelination
  • Theiler's virus

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Genetically dominant spinal cord repair in a murine model of chronic progressive multiple sclerosis. / Bieber, Allan J.; Ure, Daren R.; Rodriguez, Moses.

In: Journal of Neuropathology and Experimental Neurology, Vol. 64, No. 1, 01.2005, p. 46-57.

Research output: Contribution to journalArticle

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