Mice lacking myeloperoxidase are more susceptible to experimental autoimmune encephalomyelitis.
EAE is a demyelinating disease which serves as an animal model for multiple sclerosis (MS). Myeloperoxidase (MPO) has been implicated in MS through its presence in invading macrophages, and by association of a -463G/A promoter polymorphism with increased risk. Also, MPO at 17q23.1 is within a region identified in genome scans as a MS susceptibility locus. We here examine the incidence of EAE in MPO knockout (KO) mice. MPO is detected in invading macrophages in the CNS of wild-type mice, yet unexpectedly, MPO-KO mice have significantly increased incidence of EAE: Ninety percent of MPO-KO mice developed complete hind limb paralysis as compared to 33% of wildtype (WT) littermates (P<0.0001). This is the first evidence that MPO plays a significant role in EAE, consistent with its postulated role in MS.
Brennan
M
M
Departments of Medicine, Microbiology and Molecular Genetics and Human Genetics, UCLA, 47-123 Center for Health Sciences, Los Angeles, CA 90095, USA.
Gaur
A
A
Pahuja
A
A
Lusis
A J
AJ
Reynolds
W F
WF
D000818:Animals; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology*; D007371:Interferon-gamma / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000502:physiology; D052247:Nitric Oxide Synthase Type II; D009195:Peroxidase / Q000172:deficiency / Q000502:physiology*
D007371:Interferon-gamma; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse