Gangliosidoses are inherited lysosomal storage disorders caused by reduced or absent activity of either a lysosomal enzyme involved in ganglioside catabolism, or an activator protein required for the proper activity of a ganglioside hydrolase, which results in the intra-lysosomal accumulation of undegraded metabolites. We hereby describe morphological, ultrastructural, biochemical and genetic features of GM2 gangliosidosis in three captive bred wild boar littermates. The piglets were kept in a partially-free range farm and presented progressive neurological signs, starting at 6 months of age. Animals were euthanized at approximately one year of age due to their poor conditions. Neuropathogens were excluded as a possible cause of the signs. Gross examination showed a reduction of cerebral and cerebellar consistency. Central (CNS) and peripheral (PNS) nervous system neurons were enlarged and foamy, with severe and diffuse cytoplasmic vacuolization. Transmission electron microscopy (TEM) of CNS neurons demonstrated numerous lysosomes, filled by parallel or concentric layers of membranous electron-dense material, defined as membranous cytoplasmic bodies (MCB). Biochemical composition of gangliosides analysis from CNS revealed accumulation of GM2 ganglioside; furthermore, Hex A enzyme activity was less than 1% compared to control animals. These data confirmed the diagnosis of GM2 gangliosidosis. Genetic analysis identified, at a homozygous level, the presence of a missense nucleotide variant c.1495C > T (p Arg499Cys) in the hexosaminidase subunit alpha gene (HEXA), located within the GH20 hexosaminidase superfamily domain of the encoded protein. This specific HEXA variant is known to be pathogenic and associated with Tay-Sachs disease in humans, but has never been identified in other animal species. This is the first report of a HEXA gene associated Tay-Sachs disease in wild boars and provides a comprehensive description of a novel spontaneous animal model for this lysosomal storage disease.

神经节苷脂沉积症是遗传性溶酶体贮积症，由参与神经节苷脂分解代谢的溶酶体酶或神经节苷脂水解酶正常活性所需的激活蛋白活性降低或缺失引起，这会导致未降解代谢物在溶酶体内积聚。我们在此描述了三只圈养野猪同窝仔猪中 GM2 神经节苷脂沉积症的形态学、超微结构、生化和遗传特征。仔猪被饲养在一个部分自由放养的农场中，并从 6 个月大时开始出现进行性神经系统症状。由于动物状况不佳，动物在大约一岁时被安乐死。神经病原体被排除为这些体征的可能原因。大体检查显示大脑和小脑一致性降低。中枢 (CNS) 和外周 (PNS) 神经系统神经元增大并呈泡沫状，伴有严重和弥漫性细胞质空泡化。CNS 神经元的透射电子显微镜 (TEM) 显示出许多溶酶体，由平行或同心的膜状电子致密材料层填充，定义为膜状细胞质体 (MCB)。来自 CNS 的神经节苷脂的生化成分分析显示 GM2 神经节苷脂的积累；此外，与对照动物相比，Hex A 酶活性低于 1%。这些数据证实了 GM2 神经节苷脂沉积症的诊断。遗传分析在纯合子水平上发现，己糖胺酶亚基 α 基因中存在错义核苷酸变体 c.1495C > T (p Arg499Cys)。CNS 神经元的透射电子显微镜 (TEM) 显示出许多溶酶体，由平行或同心的膜状电子致密材料层填充，定义为膜状细胞质体 (MCB)。来自 CNS 的神经节苷脂的生化成分分析显示 GM2 神经节苷脂的积累；此外，与对照动物相比，Hex A 酶活性低于 1%。这些数据证实了 GM2 神经节苷脂沉积症的诊断。遗传分析在纯合子水平上发现，己糖胺酶亚基 α 基因中存在错义核苷酸变体 c.1495C > T (p Arg499Cys)。CNS 神经元的透射电子显微镜 (TEM) 显示出许多溶酶体，由平行或同心的膜状电子致密材料层填充，定义为膜状细胞质体 (MCB)。来自 CNS 的神经节苷脂的生化成分分析显示 GM2 神经节苷脂的积累；此外，与对照动物相比，Hex A 酶活性低于 1%。这些数据证实了 GM2 神经节苷脂沉积症的诊断。遗传分析在纯合子水平上发现，己糖胺酶亚基 α 基因中存在错义核苷酸变体 c.1495C > T (p Arg499Cys)。来自 CNS 的神经节苷脂的生化成分分析显示 GM2 神经节苷脂的积累；此外，与对照动物相比，Hex A 酶活性低于 1%。这些数据证实了 GM2 神经节苷脂沉积症的诊断。遗传分析在纯合子水平上发现，己糖胺酶亚基 α 基因中存在错义核苷酸变体 c.1495C > T (p Arg499Cys)。来自 CNS 的神经节苷脂的生化成分分析显示 GM2 神经节苷脂的积累；此外，与对照动物相比，Hex A 酶活性低于 1%。这些数据证实了 GM2 神经节苷脂沉积症的诊断。遗传分析在纯合子水平上发现，己糖胺酶亚基 α 基因中存在错义核苷酸变体 c.1495C > T (p Arg499Cys)。HEXA )，位于编码蛋白质的 GH20 己糖胺酶超家族结构域内。已知这种特定的HEXA变体具有致病性并与人类的 Tay-Sachs 病有关，但从未在其他动物物种中发现。这是野猪中HEXA基因相关 Tay-Sachs 病的第一份报告，并提供了对这种溶酶体贮积病的新型自发动物模型的全面描述。