Experimental Models Poster Presentation

P0951 - Challenge to creation of neuromyelitis optica mice model by AQP4 peptide immunization (ID 719)

Speakers
  • K. Serizawa
Authors
  • K. Serizawa
  • S. Miyake
  • H. Tomizawa-Shinohara
  • K. Yogo
  • Y. Matsumoto
Presentation Number
P0951
Presentation Topic
Experimental Models

Abstract

Background

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system mainly associated with autoantibodies against the glial water channel protein aquaporin-4 (AQP4). A number of NMOSD related animal models have recently been reported. For example, general NMOSD models are produced by peripheral injection of immunoglobulin from NMOSD patients (NMO-IgG) in experimental autoimmune encephalomyelitis mice or intra-cerebral administration of NMO-IgG with human complement in naïve mice. In addition, AQP4-specific adoptive transfer model was also reported. But AQP4 immune process is not involved in these NMOSD models. On the other hand, creation of an AQP4-immunized mice model with clinical and histologic manifestations of CNS autoimmunity has proven challenging.

Objectives

In the present study, we tried to create AQP4 peptide-induced experimental autoimmune encephalomyelitice mice as NMOSD model.

Methods

Female C57BL/6J mice were used. Mice were subcutaneously immunized with 200 μg of AQP4 p201-220 peptide emulsified in complete Freund’s adjuvant supplemented with Mycobacterium tuberculosis extract H37Ra (Day 0). Pertussis toxin (400 ng) was administered at Days 0 and 2. Mice were sequentially scored for clinical symptoms according to the following scale: 0, no disease; 1, limp tail; 2, hind limb weakness; 3, hind limb paresis; 4, hind limb paralysis; 5, hind limb and fore limb paralysis; 6, moribundity and death.

Results

Total ten mice were immunized, four of which showed clinical symptoms within Day 34; two mice were clinical score 2, the other mice were clinical score 3.

Conclusions

NMOSD like model can be created by AQP4-immunization. Now, we are conducting additional experiments to examine the detailed characterization of this model, for example histopathological profiling such as AQP4 and astrocyte pathology in the spinal cord.

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