Phenotype of arylsulfatase A-deficient mice: Relationship to human metachromatic leukodystrophy
Phenotype of arylsulfatase A-deficient mice: Relationship to human metachromatic leukodystrophy
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DOI：
10.1073/pnas.93.25.14821
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发表时间：
1996-12-10
影响因子：
11.1
通讯作者：
Gieselmann, V
中科院分区：
文献类型：
--
作者：
Hess, B;Saftig, P;Gieselmann, V
异色性脑白质营养不良是一种由芳基硫酸酯酶a缺乏引起的溶酶体鞘脂储存障碍，该疾病以进行性脱髓鞘为特征，引起各种神经系统症状，由于没有自然发生的疾病动物模型，我们产生了芳基硫酸酯酶a缺乏的小鼠。缺乏神经鞘脂的动物在各种神经元和非神经元组织中储存脑苷-3-硫酸盐。储存模式与受影响的人类相当，但在2岁之前没有观察到白质的严重缺陷。1岁小鼠轴突横截面积减少，出现星形胶质细胞增生；小胶质细胞的激活在1岁时开始，并在2岁时普遍化。浦肯野细胞树突形态改变。在听神经节中，神经元和髓鞘纤维的数量严重减少，并伴有脑干听觉诱发电位的丧失。神经系统检查显示明显的神经运动协调障碍。
Metachromatic leukodystrophy is a lysosomal sphingolipid storage disorder caused by the deficiency of arylsulfatase A, The disease is characterized by progressive demyelination, causing various neurologic symptoms, Since no naturally occurring animal model of the disease is available, we have generated arylsulfatase A-deficient mice. Deficient animals store the sphingolipid cerebroside-3-sulfate in various neuronal and nonneuronal tissues. The storage pattern is comparable to that of affected humans, but gross defects of white matter were not observed up to the age of 2 years. A reduction of axonal cross-sectional area and an astrogliosis were observed in 1-year-old mice; activation of microglia started at 1 year and was generalized at 2 years. Purkinje cell dendrites show an altered morphology. In the acoustic ganglion numbers of neurons and myelinated fibers are severely decreased, which is accompanied by a loss of brainstem auditory-evoked potentials. Neurologic examination reveals significant impairment of neuromotor coordination.