Chair of General Pathology and Neuropathology, Institute of Veterinary Pathology, Ludwig-Maximilians University of Munich, Munich, Germany.
Acta Neuropathol. 2009 Nov;118(5):697-709. doi: 10.1007/s00401-009-0548-6. Epub 2009 May 23.
Our knowledge of molecular mechanisms underlying mitochondrial disorders in humans has increased considerably during the past two decades. Mitochondrial encephalomyopathies have sporadically been reported in dogs. However, molecular and biochemical data that would lend credence to the suspected mitochondrial origin are largely missing. This study was aimed to characterise a Leigh-like subacute necrotising encephalopathy (SNE) in Yorkshire Terriers and to shed light on its enzymatic and genetic background. The possible resemblance to SNE in Alaskan Huskies and to human Leigh syndrome (LS) was another focus of interest. Eleven terriers with imaging and/or gross evidence of V-shaped, non-contiguous, cyst-like cavitations in the striatum, thalamus and brain stem were included. Neuropathological examinations focussed on muscle, brain pathology and mitochondrial ultrastructure. Further investigations encompassed respiratory-chain activities and the mitochondrial DNA. In contrast to mild non-specific muscle findings, brain pathology featured the stereotypic triad of necrotising grey matter lesions with relative preservation of neurons in the aforementioned regions, multiple cerebral infarcts, and severe patchy Purkinje-cell degeneration in the cerebellar vermis. Two dogs revealed a reduced activity of respiratory-chain-complexes I and IV. Genetic analyses obtained a neutral tRNA-Leu(UUR) A-G-transition only. Neuropathologically, SNE in Yorkshire Terriers is nearly identical to the Alaskan Husky form and very similar to human LS. This study, for the first time, demonstrated that canine SNE can be associated with a combined respiratory chain defect. Mitochondrial tRNA mutations and large genetic rearrangements were excluded as underlying aetiology. Further studies, amongst relevant candidates, should focus on nuclear encoded transcription and translation factors.
在过去的二十年中，我们对人类线粒体疾病的分子机制的了解有了相当大的提高。散发性犬线粒体脑肌病已有报道。然而，支持怀疑的线粒体起源的分子和生化数据在很大程度上仍然缺乏。本研究旨在描述约克夏梗犬中 Leigh 样亚急性坏死性脑脊髓病（SNE），并阐明其酶学和遗传背景。另一个关注的焦点是其与阿拉斯加雪橇犬中的 SNE 和人类 Leigh 综合征（LS）的相似性。研究共纳入了 11 只具有影像学和/或大体证据的犬，显示纹状体、丘脑和脑干存在 V 形、非连续、囊状空化。神经病理学检查主要集中在肌肉、脑病理学和线粒体超微结构上。进一步的研究包括呼吸链活性和线粒体 DNA。与轻度非特异性肌肉表现不同，脑病理学的特征是上述区域坏死性灰质病变与神经元相对保存、多发性脑梗死以及小脑蚓部浦肯野细胞严重斑片状变性的典型三联征。其中 2 只犬显示呼吸链复合物 I 和 IV 的活性降低。遗传分析仅获得中性 tRNA-Leu（UUR）A-G 转换。神经病理学上，约克夏梗犬的 SNE 与阿拉斯加雪橇犬形式几乎相同，与人类 LS 非常相似。本研究首次证明犬 SNE 可与复合呼吸链缺陷相关。排除了线粒体 tRNA 突变和大片段基因重排作为潜在的病因。进一步的研究，应在相关候选者中，重点关注核编码转录和翻译因子。
