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Spontaneous opticospinal encephalomyelitis in a double-transgenic mouse model of autoimmune T cell/B cell cooperation
Gurumoorthy Krishnamoorthy, … , Hartmut Wekerle, Andreas Holz
Gurumoorthy Krishnamoorthy, … , Hartmut Wekerle, Andreas Holz
Published September 1, 2006
Citation Information: J Clin Invest. 2006;116(9):2385-2392. https://doi.org/10.1172/JCI28330.
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Research Article Autoimmunity

Spontaneous opticospinal encephalomyelitis in a double-transgenic mouse model of autoimmune T cell/B cell cooperation

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Abstract

We describe a double-transgenic mouse strain (opticospinal EAE [OSE] mouse) that spontaneously develops an EAE-like neurological syndrome closely resembling a human variant of multiple sclerosis, Devic disease (also called neuromyelitis optica). Like in Devic disease, the inflammatory, demyelinating lesions were located in the optic nerve and spinal cord, sparing brain and cerebellum, and the murine lesions showed histological similarity with their human correlates. OSE mice have recombination-competent immune cells expressing a TCR-αβ specific for myelin oligodendrocyte glycoprotein (MOG) aa 35–55 peptide in the context of I-Ab along with an Ig J region replaced by the recombined heavy chain of a monoclonal antibody binding to a conformational epitope on MOG. OSE mouse B cells bound even high dilutions of recombinant MOG, but not MOG peptide, and processed and presented it to autologous T cells. In addition, in OSE mice, but not in single-transgenic parental mice, anti-MOG antibodies were switched from IgM to IgG1.

Authors

Gurumoorthy Krishnamoorthy, Hans Lassmann, Hartmut Wekerle, Andreas Holz

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Figure 2

Histological analysis of the CNS from sick OSE mice.

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Histological analysis of the CNS from sick OSE mice.
(A–J and L–O) The o...
(A–J and L–O) The optic nerves (A–F) and spinal cords (G–J and L–O) from OSE mice that developed neurological disease in a non-SPF environment showed severe infiltration, demyelination, and axonal damage as visualized by H&E (A, D, G, and I), luxol fast blue (B, E, H, and J), and Bielschowsky silver impregnation (C and F). Arrows in G indicate eosinophilic granulocytes. (K) Demyelinating lesions (red shading) were specifically localized in the optic nerves and spinal cords of OSE mice, thus resembling the lesion distribution observed in human Devic disease. Cervical sections are labeled C1–C8; thoracic sections are labeled T1–T13; lumbar sections of the spinal cord are labeled L1–L7. (L–O) Cellular infiltrates were predominantly composed of CD11b+ macrophages/microglia (L) and CD4+ T cells (M), while only few CD8+ T (N) and B cells (O) were found exclusively in the optic nerves and spinal cords of sick mice. Note that healthy OSE littermates remained free of demyelinating CNS lesions (see Supplemental Figure 3). Furthermore, OSE mice housed under SPF conditions showed slightly stronger infiltration/demyelination (see Supplemental Figure 4).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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