Pathogenesis of axonal dystrophy and demyelination in alphaA-crystallin-expressing transgenic mice

We recently described a transgenic mouse strain overexpressing hamster alphaA-crystallin, a small heat shock protein, under direction of the hamster vimentin promoter. As a result myelin was degraded and axonal dystrophy in both central nervous system (especially spinal cord) and peripheral nervous...

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Bibliographic Details
Published in:International journal of experimental pathology 2003-04, Vol.84 (2), p.91-99
Main Authors: Van Rijk, A F, Sweers, M A M, Merkx, G F M, Lammens, M, Bloemendal, H
Format: Article
Language:English
Subjects:
alpha-Crystallin A Chain - metabolism
Animals
Blood Glucose - metabolism
Blotting, Southern
Blotting, Western
Catalase - metabolism
Demyelinating Diseases - etiology
Demyelinating Diseases - genetics
Demyelinating Diseases - metabolism
Disease Models, Animal
Mice
Mice, Transgenic
Myelin P0 Protein - metabolism
Neuroaxonal Dystrophies - etiology
Neuroaxonal Dystrophies - genetics
Neuroaxonal Dystrophies - metabolism
Superoxide Dismutase - metabolism
Transglutaminases - metabolism
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Summary:We recently described a transgenic mouse strain overexpressing hamster alphaA-crystallin, a small heat shock protein, under direction of the hamster vimentin promoter. As a result myelin was degraded and axonal dystrophy in both central nervous system (especially spinal cord) and peripheral nervous system occurred. Homozygous transgenic mice developed hind limb paralysis after 8 weeks of age and displayed progressive loss of myelin and axonal dystrophy in both the central and peripheral nervous system with ongoing age. Pathologically the phenotype resembled, to a certain extent, neuroaxonal dystrophy. The biochemical findings presented in this paper (activity of the enzymes superoxide dismutase, catalase and transglutamase, myelin protein zero expression levels and blood sugar levels) confirm this pathology and exclude other putative pathologies like Amyothrophic Lateral Sclerosis and Hereditary Motor and Sensory Neuropathy. Consequently, an excessive cytoplasmic accumulation of the transgenic protein or a disturbance of the normal metabolism are considered to cause the observed neuropathology. Therefore, extra-ocular alphaA-crystallin-expressing transgenic mice may serve as a useful animal model to study neuroaxonal dystrophy.
ISSN:0959-9673