Establishment of animal models of lysosomal storage diseases and prevention of those diseases outside the laboratory

1.本文介绍了一种快速简便的诊断方法。使用该方法，在日本和海外进行了分子调查，以启动预防措施。分析了本病的MRI表现特点。此外，测定脑脊液中显示神经变性程度的生物标志物。使用这些生物标志物，证明糖皮质激素治疗对GM 1神经节苷脂沉积症无效。本文研究了山德霍夫病犬的MRI表现特征。而在犬HEXB基因外显子序列中未检测到突变.日本家猫山德霍夫病（Sandhoff disease）的MR 1影像特征。在猫HEXB基因中可以确定致病突变，并开展了分子检测。分子调查表明，这种突变在日本家猫群体中广泛传播.边境牧羊犬的蜡样脂褐质沉积症与民间组织日本边境牧羊犬健康网络合作，在日本各地开发了DNA测定法并进行了分子调查。该活性表明该疾病的携带者频率为4 - 5%，并且该活性可以有效地预防该疾病。5.日本黑犊牛的溶酶体病对犊牛器官中的储存物质的分析表明，该物质可能是唾液酸结合的寡糖和GM 3神经节苷脂。提示该病可能为半乳糖唾液酸沉积症或唾液酸沉积症。然而，在与这些候选疾病相关的两个基因上没有发现突变。

1.GMI gangliosidosis in shiba dogsThe diagnostic method was developed to be more rapid and easier one. Using the method, a molecular survey was performed to start preventive measure in Japan and overseas. The characteristics in MRI imaging in this disease were determined. In addition, the biomarkers in cerebrospinal fluid to show the degree of neurodeneration were determined. Using these biomarkers, it was demonstrated that a glucocorticoid therapy is not efficient for GM1 gangliosidosis.2. Sandhoff disease in a gorden retrieverThe characteristics in MRI imaging in canine Sandhoff disease were determined. However, no mutations were detected in the sequence of exons of canine HEXB gene.3. Sandhoff disease in Japanese domestic catsThe characteristics in MR1 imaging in feline Sandhoff disease were determined. The causative mutation could be identified in the feline HEXB gene, and the molecular test was developed. The molecular survey suggested that this mutation is widely spread in the Japanese domestic cat population.4. Ceroid-lipofuscinosis in border colliesThe DNA assay was developed and a molecular survey was performed all over Japan in partnership with a civilian organization, Japan Border Collie Health Network. This activity demonstrated that a carrier frequency of this disease is 4 to 5% and the activity can be effective for prevention of this disease.5.Lysosomal disease in a Japanese black calfThe analysis of storage materials in organs of the calf showed that the Materials might be sialic acids-bound oligosaccharides and GM3 ganglioside. This result suggested that the disease might be galactosialidosis or sialidosis. However, no mutations were found on two genes related to these candidate diseases.