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

1.为柴犬GMI神经节脂质沉积症的诊断提供了一种快速、简便的方法。利用该方法，在日本和国外进行了分子调查，以启动预防措施。确定本病的MRI影像学特征。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GM1神经节脂质中毒无效。犬山德霍夫病的MRI表现特点。然而，犬HEXB基因外显子序列未检测到突变。日本家猫的山德霍夫病研究了山德霍夫病的MR1影像学特征。在猫的HEXB基因中发现了致病突变，并建立了分子检测方法。分子调查表明，该突变在日本家猫种群中广泛存在。边境牧羊犬的Ceroid-lipofuscinosis与民间组织日本边境牧羊犬健康网络合作，开发了DNA测定方法，并在日本各地进行了分子调查。该活性表明该疾病的携带频率为4 ~ 5%，该活性可有效预防该疾病。对犊牛脏器内储存物质的分析表明，这些物质可能是唾液酸结合寡糖和GM3神经节苷脂。提示该疾病可能为半乳糖唾液中毒或唾液中毒。然而，没有发现与这些候选疾病相关的两个基因突变。

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.