1 School of Veterinary Science, Massey University, Palmerston North, New Zealand.
2 Childhood Dementia Research Group, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
Vet Pathol. 2019 Sep;56(5):743-748. doi: 10.1177/0300985819839239. Epub 2019 Apr 14.
A neurological disease was investigated in 3 German Shepherd pups from the same litter that failed to grow normally, appeared stiff, were reluctant to move, and were deaf. They developed intermittent seizures and ataxia and had proprioceptive defects. Histopathology showed severe vacuolation of neurons, astrocytes in nervous tissue, renal tubular epithelial cells, and macrophages in nervous tissue, spleen, and liver. Vacuoles appeared empty with no storage material stained by periodic acid-Schiff (PAS) or Sudan black stains, leading to a diagnosis of a lysosomal storage disease and in particular an oligosaccharidosis. Biochemical and genomic studies showed that this was β-mannosidosis, not previously diagnosed in dogs. A c.560T>A transition in exon 4 of the gene was found, which segregated in these and other family members in a manner consistent with it being the causative mutation of an autosomal recessive disease. This mutation led to substitution of isoleucine to asparagine at position 187 of the 885 amino acid enzyme, a change expected to have functional significance.
对来自同一窝的 3 只德国牧羊犬幼犬进行了一项神经疾病研究，这 3 只幼犬生长异常、行动僵硬、不愿移动且失聪。它们出现间歇性癫痫发作和共济失调，且本体感觉有缺陷。组织病理学检查显示，神经元、神经组织中的星形胶质细胞、肾小管上皮细胞以及神经组织、脾脏和肝脏中的巨噬细胞中存在严重的空泡化。空泡经过过碘酸雪夫（PAS）或苏丹黑染色后显示为空泡，没有储存物质，因此诊断为溶酶体贮积症，特别是寡糖贮积症。生化和基因组研究表明，这是β-甘露糖苷症，此前在犬中尚未诊断出。在该基因的外显子 4 中发现了 c.560T>A 转换，该突变以与常染色体隐性疾病一致的方式在这些犬及其它家族成员中发生遗传，这一突变导致第 187 位的异亮氨酸被天冬酰胺取代，这一改变预计具有功能意义。
