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

• Published in: International journal of experimental pathology Vol. 84; no. 2; pp. 91 - 99
• Main Authors: Van Rijk, A.F., Sweers, M.A.M., Merkx, G.F.M., Lammens, M., Bloemendal, H.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.04.2003; Blackwell Science; Blackwell Science Inc
• Subjects: Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Medical sciences; Neurology; Original; Immunohistochemistry; Animal model; Nervous system diseases; Biochemical analysis; Rodentia; Transgenic animal; Neuroaxonal dystrophy; Cerebral disorder; Genetic disease; Pathology; Vertebrata; Experimental disease; Mammalia; Crystallin; Mouse; Demyelination; Animal; Central nervous system disease; Degenerative disease; Molecular biology; Immunofluorescence
• ISSN: 0959-9673; 1365-2613
• DOI: 10.1046/j.1365-2613.2003.00340.x

We recently described a transgenic mouse strain overexpressing hamster αA‐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 αA‐crystallin‐expressing transgenic mice may serve as a useful animal model to study neuroaxonal dystrophy.