Delaney K H, Kwiecien J M, Wegiel J, Wisniewski H M, Percy D H, Fletch A L
McMaster University Central Animal Facility, Hamilton, Ontario, Canada.
Lab Anim Sci. 1995 Oct;45(5):547-53.
Tremors were observed in 15 Long Evans rats beginning at 10 to 12 days of age. These were followed by progressively worsening ataxia, hind limb paresis, episodes of immobility, and seizures by 5 to 14 weeks. Gross lesions were not observed at necropsy in rats euthanized and perfused at 4 to 16 weeks of age. Neurohistologic examination revealed dysmyelination in the central nervous system. Astrogliosis in the white matter with marked increase of expression of the glial fibrillary acid protein 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 cerebellar white matter, midbrain, and thalamus of rats over 6 weeks old. Neuronal degeneration and loss was evident in the cortex, hippocampus, 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 remarkable survival period and appears to have an autosomal recessive mode of inheritance.
在15只Long Evans大鼠中观察到震颤，始于10至12日龄。随后，在5至14周时，共济失调逐渐加重，后肢轻瘫、静止发作和癫痫发作也随之出现。在4至16周龄时安乐死并灌注的大鼠尸检中未观察到明显病变。神经组织学检查显示中枢神经系统存在髓鞘形成异常。白质中的星形胶质细胞增生，胶质纤维酸性蛋白标志物的表达显著增加，同时伴有弥漫性小胶质细胞增生。散在的胶质细胞，被认为是少突胶质细胞，含有微小的过碘酸希夫阳性细胞质颗粒。在6周龄以上大鼠的小脑白质、中脑和丘脑中观察到大型矿化的过碘酸希夫阳性和层状结构。皮质、海马和中脑出现明显的神经元变性和丢失。在脊髓腹侧和外侧索中发现大型轴突球。对四只患病大鼠的超微结构研究显示，几乎完全没有有髓轴突和正常的髓鞘，少突胶质细胞发生变性和坏死。Long Evans震颤大鼠代表一种新型的髓鞘突变体，具有显著的生存期，似乎具有常染色体隐性遗传模式。
