A comparative study of experimental mouse models of central nervous system demyelination.
Several mouse models of multiple sclerosis (MS) are now available. We have established a mouse model, in which ocular infection with a recombinant HSV-1 that expresses murine interleukin (IL)-2 constitutively (HSV-IL-2) causes central nervous system demyelination in different strains of mice. This model differs from most other models, in which it represents a mixture of viral and immune triggers. In the present study, we directly compared MOG35-55, MBP35-47 and PLP190-209 models of experimental autoimmune encephalitis with our HSV-IL-2-induced MS model. Mice with HSV-IL-2- and myelin oligodendrocyte glycoprotein (MOG)-induced demyelinating diseases demonstrated a similar pattern and distribution of demyelination in their brain, spinal cord (SC) and optic nerves (ONs). In contrast, no demyelination was detected in the ONs of myelin basic protein (MBP)- and proteolipid protein (PLP)-injected mice. Interferon-β (IFN-β) injections significantly reduced demyelination in brains of all groups, in the SCs of the MOG and MBP groups, and completely blocked it in the SCs of the PLP and HSV-IL-2 groups as well as in ONs of MOG and HSV-IL-2 groups. In contrast to IFN-β treatment, IL-12p70 protected the HSV-IL-2 group from demyelination, whereas IL-4 was not effective at all in preventing demyelination. MOG-injected mice showed clinical signs of paralysis and disease-related mortality, whereas mice in the other treatment groups did not. Collectively, the results indicate that the HSV-IL-2 model and the MOG model complement each other and, together, provide unique insights into the heterogeneity of human MS.
Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
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OM
Dumitrascu
Center for Neurobiology and Vaccine Development-D2066, Ophthalmology Research, Department of Surgery, Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
K R
KR
Mott
Center for Neurobiology and Vaccine Development-D2066, Ophthalmology Research, Department of Surgery, Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
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Ghiasi
D000818:Animals; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology*; D003711:Demyelinating Diseases / Q000209:etiology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D005260:Female; D018259:Herpesvirus 1, Human / Q000235:genetics; D016899:Interferon-beta / Q000494:pharmacology; D018664:Interleukin-12 / Q000494:pharmacology; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000494:pharmacology; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000209:etiology*; D018991:Myelin Proteolipid Protein / Q000494:pharmacology; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity
D007376:Interleukin-2; D018991:Myelin Proteolipid Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D018664:Interleukin-12; D015847:Interleukin-4; D016899:Interferon-beta