Sango K, Yamanaka S, Hoffmann A, Okuda Y, Grinberg A, Westphal H, McDonald M P, Crawley J N, Sandhoff K, Suzuki K, Proia R L
Section on Biochemical Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nat Genet. 1995 Oct;11(2):170-6. doi: 10.1038/ng1095-170.
Tay-Sachs and Sandhoff diseases are clinically similar neurodegenerative disorders. These two sphingolipidoses are characterized by a heritable absence of beta-hexosaminidase A resulting in defective GM2 ganglioside degradation. Through disruption of the Hexa and Hexb genes in embryonic stem cells, we have established mouse models corresponding to each disease. Unlike the two human disorders, the two mouse models show very different neurologic phenotypes. Although exhibiting biochemical and pathologic features of the disease, the Tay-Sachs model showed no neurological abnormalities. In contrast, the Sandhoff model was severely affected. The phenotypic difference between the two mouse models is the result of differences in the ganglioside degradation pathway between mice and humans.
泰-萨克斯病和桑德霍夫病是临床上相似的神经退行性疾病。这两种鞘脂类疾病的特征是遗传性缺乏β-己糖胺酶A，导致GM2神经节苷脂降解缺陷。通过破坏胚胎干细胞中的Hexa和Hexb基因，我们建立了与每种疾病对应的小鼠模型。与这两种人类疾病不同，这两种小鼠模型表现出非常不同的神经表型。尽管泰-萨克斯病模型表现出该疾病的生化和病理特征，但未显示出神经异常。相比之下，桑德霍夫病模型受到严重影响。这两种小鼠模型之间的表型差异是小鼠和人类神经节苷脂降解途径不同的结果。
