Tubulinopathies are a group of recently described diseases characterized by mutations in the tubulin genes. Mutations in TUBB4A produce diseases such as dystonia type 4 (DYT4) and hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC), which are clinically diagnosed by magnetic resonance imaging (MRI). We propose the taiep rat as the first animal model for tubulinopathies. The spontaneous mutant suffers from a syndrome related to a central leukodystrophy and characterized by tremor, ataxia, immobility, epilepsy, and paralysis. The pathological signs presented by these rats and the morphological changes we found by our longitudinal MRI study are similar to those of patients with mutations in TUBB4A. The diffuse atrophy we found in brain, cerebellum and spinal cord is related to the changes detectable in many human tubulinopathies and in particular in H-ABC patients, where myelin degeneration at the level of putamen and cerebellum is a clinical trademark of the disease. We performed Tubb4a exon analysis to corroborate the genetic defect and formulated hypotheses about the effect of amino acid 302 change on protein physiology. Optical microscopy of taiep rat cerebella and spinal cord confirmed the optical density loss in white matter associated with myelin loss, despite the persistence of neural fibers.

中文翻译：

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H-ABC 肾小管病大鼠模型的 MRI 特征

微管蛋白病是一组最近描述的以微管蛋白基因突变为特征的疾病。TUBB4A 中的突变会产生诸如 4 型肌张力障碍 (DYT4) 和伴有基底神经节和小脑萎缩 (H-ABC) 的髓鞘形成不足等疾病，这些疾病可通过磁共振成像 (MRI) 进行临床诊断。我们建议 taiep 大鼠作为微管蛋白病的第一个动物模型。自发突变体患有与中枢性脑白质营养不良相关的综合征，其特征是震颤、共济失调、不动、癫痫和瘫痪。这些大鼠的病理征象和纵向MRI研究发现的形态学变化与TUBB4A突变患者相似。我们在大脑中发现的弥漫性萎缩，小脑和脊髓与许多人类微管蛋白病，特别是 H-ABC 患者中可检测到的变化有关，其中壳核和小脑水平的髓鞘变性是该疾病的临床标志。我们进行了 Tubb4a 外显子分析以证实遗传缺陷，并提出了关于氨基酸 302 变化对蛋白质生理学影响的假设。taiep 大鼠小脑和脊髓的光学显微镜证实了与髓鞘损失相关的白质中的光密度损失，尽管神经纤维仍然存在。我们进行了 Tubb4a 外显子分析以证实遗传缺陷，并提出了关于氨基酸 302 变化对蛋白质生理学影响的假设。taiep 大鼠小脑和脊髓的光学显微镜证实了与髓鞘损失相关的白质中的光密度损失，尽管神经纤维仍然存在。我们进行了 Tubb4a 外显子分析以证实遗传缺陷，并提出了关于氨基酸 302 变化对蛋白质生理学影响的假设。taiep 大鼠小脑和脊髓的光学显微镜证实了与髓鞘损失相关的白质中的光密度损失，尽管神经纤维仍然存在。