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Abstract：
Canavan disease (CD) is a fatal hereditary neurological disorder caused by a mutation in the aspartoacylase (ASPA) gene and characterized by neurological signs and vacuolation in the central nervous system (CNS). The mutation inhibits the hydrolysis of N-acetyl-aspartate (NAA) resulting in accumulation of NAA in the CNS. A new Aspa-knockout rat was generated by transcription activator-like effector nuclease (TALEN) technology. Herein we describe the pathological and morphometrical findings in the brain and spinal cords of Aspa-knockout rats. Although Aspa-knockout rats did not show any neurological signs, vacuolation with swollen axons, hypomyelination, and activated swollen astrocytes were observed mainly in the brainstem reticular formation, ascending and descending motor neuron pathway, and in the olfactory tract. Morphometrical analysis revealed no obvious change in the number of neurons. These changes in the CNS are similar to human CD, suggesting that this animal model would be useful for further study of treatment and understanding the pathophysiology of human CD.
摘要：
Canavan病（CD）是一种致命的遗传性神经系统疾病，由天冬氨酸酰化酶（ASPA）基因突变引起，其特征是中枢神经系统（CNS）的神经系统体征和空泡化。该突变抑制N-乙酰天冬氨酸(NAA)的水解,导致NAA在CNS中的积累。通过转录激活因子样效应核酸酶（TALEN）技术产生了一种新的Aspa基因敲除大鼠。在此，我们描述了Aspa基因敲除大鼠的大脑和脊髓中的病理和形态计量学发现。尽管Aspa基因敲除的大鼠没有表现出任何神经系统症状，轴突肿胀的空泡，髓鞘减少,活化的星形胶质细胞主要在脑干网状结构中观察到，上升和下降运动神经元通路，在嗅觉区。形态计量学分析显示神经元数量没有明显变化。中枢神经系统的这些变化与人类CD相似，这表明该动物模型将有助于进一步研究治疗和理解人类CD的病理生理学。
