Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Departamento de Fisiología, Biofísica y Neurociencias, 07360 México DF, México.
Neurotherapeutics. 2012 Apr;9(2):285-96. doi: 10.1007/s13311-012-0117-x.
Machado-Joseph disease, also called spinocerebellar ataxia type 3 (MJD/SCA3), is a hereditary and neurodegenerative movement disorder caused by ataxin-3 with a pathological polyglutamine stretch (mutant ataxin-3). Seven transgenic mouse models expressing full-length human mutant ataxin-3 throughout the brain have been generated and are compared in this review. They vary in the corresponding transgenic DNA constructs with differences that include the encoded human ataxin-3 isoform(s), number of polyglutamine(s), and the promoter driving transgene expression. The behaviors/signs evaluated in most models are body weight, balance/coordination, locomotor activity, gait, limb position, and age at death. The pathology analyzed includes presence of neuronal intranuclear inclusions, and qualitative evidence of neurodegeneration. On the basis of striking similarities in age-range of detection and number of behavior/sign abnormalities and pathology, all but 1 mouse model could be readily sorted into groups with high, intermediate, and low severity of phenotype. Stereological analysis of neurodegeneration was performed in the same brain regions in 2 mouse models; the corresponding results are consistent with the classification of the mouse models.
马查多-约瑟夫病，又称脊髓小脑共济失调 3 型（MJD/SCA3），是一种遗传性和神经退行性运动障碍，由带有病理多聚谷氨酰胺延伸（突变型 ataxin-3）的 ataxin-3 引起。本综述比较了 7 种在大脑中表达全长人突变型 ataxin-3 的转基因小鼠模型。它们在相应的转基因 DNA 构建体中存在差异，包括编码的人类 ataxin-3 同工型、多聚谷氨酰胺的数量以及驱动转基因表达的启动子。大多数模型评估的行为/体征包括体重、平衡/协调、运动活性、步态、肢体位置和死亡年龄。分析的病理学包括神经元核内包涵体的存在和神经退行性变的定性证据。基于在检测范围内年龄和行为/体征异常及病理学数量的惊人相似性，除 1 种小鼠模型外，所有模型都可以很容易地分为高、中、低严重程度表型组。在 2 种小鼠模型中对相同脑区的神经退行性变进行了体视学分析；相应的结果与小鼠模型的分类一致。
