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Rat Strain Models

Experimental Autoimmune Encephalomyelitis – A Model for Multiple Sclerosis

Experimental autoimmune encephalomyelitis (EAE) is an autoimmune demyelinating disease that is induced in several ways in rat and mouse and is commonly used as a model of multiple sclerosis. Myelin oligodendrocyte glycoprotein (MOG) induced EAE produces a range of phenotypes which closely mimic human Multiple Sclerosis. These include prominent demyelination, axonal damage and chronic relapsing disease (Becanovic et al, 2003; PMID:12517974). As in MS, the highest rat of axonal injury is found during active demylelination with a low but significant amount also found in inactive demyelination plaques (Kornek et al, 2000; PMID:10880396)

Induction Agents

  • Spinal cord homogenate
  • Myelin proteolipid protein (PLP)
  • Myelin oligodendrocyte glycoprotein (MOG) – effects include prominent demyelination, axonal damage and chronic relapsing disease (Becanovic et al, 2003 PMID:12517974)
  • Myelin oligodendrocyte basic protein
  • Myelin basic protein (MBP) (Myelin membrane encephalitogenic protein)
  • Myelin-associated glycoprotein (MAG)

Adjuvant Commonly Used with Induction Agents

  • Freund’s adjuvant (CFA)
  • Induction has also been accomplished without use of an adjuvant (Stosic-Grujicic et all, 2004 (PMID:15030513)

DISEASE COURSE

The disease course can be defined as relapsing/remitting, monophasic, acute lethal, primary progressive (Becanovic et al 2003; PMID:12517974)
 

PHENOTYPE INDICES

Weakness and Paralysis
Researchers often use a 5-point index for clinical assessment of EAE in rats although some researchers have expanded this. Descriptions and numbering vary from researcher to researcher, but generally follow these guidelines.
Index Details

Demyelination
Inflammatory demyelinating lesions found in CNS and can be present in the absence of weakness, paralysis or other neurological manifestations (Dahlman et al, 1999; PMID:10072499). A four-point scale is sometimes used: 1 = perivascular/subpial demyelination, 2 = marked demyelination, 3  extended demyelination (more than half of the spinal cord white matter or one optic nerve or more than half of the cerebellar white matter), 4 = full demyelination of the spinal cord white matter, or both optic nerves or the cerebellar white matter (Becanovic et al, 2003, PMID:12517974)

Inflammatory response in CNS
Can occur withoutweakness, paralysis or other neurological manifestations (Dahlman et al, 1999, PMID:10072499)

Perivascular mononuclear infiltrates – may be quantitated by counting inflammatory foci with 20 or more aggregated mononuclear cells – indexed by 0 = no infiltrates, 1 = less than 10 inflammatory foci with 20 or more aggregated mononuclear cells, 2 = 11-30 foci 3 = more than 30 foci
T cell infiltration – both CD8+ and CD4+ T cells present in spinal cord tissue
Perivascular deposition of immunoglobulins

Researchers sometimes use a 4-point index for histological assessment of EAE in rats.
Index Details

STRAIN MODELS

Susceptible

DA/Han (RGD strain report)

  • perivenous inflammation restricted to CNS associated with primary demyelination resulting in large confluent demyelinated plaques; higher serum levels of anti-MOG IgG, IgG2a, IgG2b, IgG2c than ACI/SegHsd (Dahlman et al, 1999, PMID:10072499)
  • develop paralysis with two to three relapses (Bergsteinsdottir et al, 2000, PMID:10640775)
  • emiparalysis, relapsing/remitting disease in ~70% in MOG induced disease (Jagodic et al, 2004, (PMID15240732)
    Phenotype report

DA.ACI (D10Rat2-D10Rat29) (RGD strain report)

    Phenotype report

DA.ACI (D10Rat15-D10Rat29) (RGD strain report)

    Phenotype report

DA.ACI (D10Rat2-D10Rat6) (RGD strain report)

    Phenotype report

DA.ACI (D10Rat219-D10Rat29) (RGD strain report)

    Phenotype report

DA.ACI (D10Rat10-D10Rat142) (RGD strain report)

    Phenotype report

DA.ACI (D10Rat12-D10Rat144) (RGD strain report)

    Phenotype report

LEW (RGD strain report)

    Phenotype report

LEW.1AV1 (RGD strain report)

  • high demyelination and inflammation indices with MOG induction, acute lethal 25%; monophasic 19%; relapsing/remitting 33%; primary progressive 6.3%, impaired balance 8.3% (Becanovic et al, 2003; PMID:12517974)
    Phenotype report

Resistant

ACI/SegHsd (RGD strain report)

  • 1/21 showed demyelination with 50µrMOG(aa 1-125) and spinal cord lesions (Dahlman et al, 1999, PMID:10072499)
  • E3/Han (RGD strain report)

  • 0/15 incident rate with spinal cord homogenate (Bergsteinsdottir et al, 2000, PMID:10640775)
  • BN (RGD strain report)

  • 0/9 incident rate with 10 mg myelin/ml (Roth et al, 1999,PMID:9973459)
  • LER (RGD strain report)

  • Resistant to active induction of EAE but susceptible to transferred EAE when injected with encephalitogenic T cells ( Blankenhorn et al, 1995, PMID:751054)
  • PVG.1AV1 (RGD strain report)

  • 4/61 incident rate with 20µrMOG(aa 1-125) (Becanovic et al, 2003, PMID:12517974)
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