FAMILIAL DYSMYELINATION IN A LONG-EVANS RAT MUTANT

Tremors were observed in 15 Long Evans rats beginning at 10 to 12 days of age. These were followed by progressively worsening ataxia, hind l imb paresis, episodes of immobility, and seizures by 5 to 14 weeks. Gr oss lesions were not observed at necropsy in rats euthanized and perfu sed at 4 to 16 weeks of age. Neurohistologic examination revealed dysm yelination in the central nervous system. Astrogliosis in the white ma tter with marked increase of expression of the glial fibrillary acid p rotein marker was accompanied by diffuse microgliosis. Scattered glial . cells, interpreted to be oligodendrocytes, contained minute periodic acid-Schiff-positive cytoplasmic granules. Large mineralized periodic acid-Schiff-positive and laminated structures were observed in the ce rebellar white matter, midbrain, and thalamus of rats over 6 weeks old . Neuronal degeneration and loss was evident in the cortex, hippocampu s, and midbrain, Large axonal spheroids were found in the ventral and lateral funiculi of the spinal cord. An ultrastructural study of four affected rats revealed an almost complete absence of myelinated axons and normal sheaths, and degeneration and necrosis of oligodendrocytes. The Long Evans shaker rat represents a novel myelin mutant with a rem arkable survival period and appears to have an autosomal recessive mod e of inheritance.