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Mice lacking myeloperoxidase are more susceptible to experimental autoimmune encephalomyelitis
1Departments of Medicine, Microbiology and Molecular Genetics and Human Genetics, UCLA, 47-123 Center for Health Sciences, Los Angeles, CA 90095, USA.
Abstract:
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.
Insights
Myeloperoxidase (MPO) deficiency unexpectedly increases the incidence of experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS). MPO knockout mice showed significantly higher rates of paralysis, indicating MPO plays a protective role in this demyelinating disease.
Area of Science:
- Neuroimmunology
- Demyelinating Diseases
- Animal Models of Neurological Disorders
Background:
- Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model for multiple sclerosis (MS).
- Myeloperoxidase (MPO) has been implicated in MS pathogenesis, with its presence noted in infiltrating macrophages and a specific promoter polymorphism linked to increased disease risk.
- The MPO gene locus (17q23.1) is situated within a region identified as a susceptibility locus for MS in genome-wide scans.
Purpose of the Study:
- To investigate the role of Myeloperoxidase (MPO) in the development of experimental autoimmune encephalomyelitis (EAE) by examining EAE incidence in MPO knockout (KO) mice.
- To determine if the absence of MPO influences disease severity and progression in an animal model relevant to multiple sclerosis (MS).
Main Methods:
- Generation and utilization of MPO knockout (KO) mice to study EAE.
- Induction of EAE in both MPO-KO and wild-type (WT) littermate mice.
- Assessment and comparison of EAE incidence, characterized by hind limb paralysis, between MPO-KO and WT groups.
Main Results:
- Myeloperoxidase (MPO) was detected in macrophages infiltrating the central nervous system (CNS) of wild-type (WT) mice during EAE.
- MPO knockout (KO) mice exhibited a significantly increased incidence of EAE compared to WT littermates.
- Ninety percent of MPO-KO mice developed complete hind limb paralysis, versus 33% of WT mice (P<0.0001).
Conclusions:
- This study provides the first evidence that Myeloperoxidase (MPO) plays a significant role in the pathogenesis of EAE.
- The findings suggest that MPO may have a protective effect in EAE, contrary to its previously postulated role in MS.
- The results warrant further investigation into the specific mechanisms by which MPO influences demyelinating diseases like MS.