MOUSE MODELS OF TAY-SACHS AND SANDHOFF DISEASES DIFFER IN NEUROLOGIC PHENOTYPE AND GANGLIOSIDE METABOLISM
MOUSE MODELS OF TAY-SACHS AND SANDHOFF DISEASES DIFFER IN NEUROLOGIC PHENOTYPE AND GANGLIOSIDE METABOLISM
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DOI：
10.1038/ng1095-170
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发表时间：
1995-10-01
期刊：
影响因子：
30.8
通讯作者：
PROIA, RL
中科院分区：
文献类型：
--
作者：
SANGO, K;YAMANAKA, S;PROIA, RL
Tay-Sachs和Sandhoff病是临床上相似的神经退行性疾病。这两种鞘脂病的特征在于β-氨基己糖苷酶A的遗传性缺失，导致G（M2）神经节苷脂降解缺陷。通过破坏胚胎干细胞中的Hexa和Herb基因，我们建立了对应于每种疾病的小鼠模型，与这两种人类疾病不同，这两种小鼠模型显示出非常不同的神经表型。虽然表现出疾病的生化和病理特征，但Tay-Sachs模型未显示出神经异常。相比之下，Sandhoff模型受到严重影响。两种小鼠模型之间的表型差异是小鼠和人类之间神经节苷脂降解途径差异的结果。
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 G(M2) ganglioside degradation. Through disruption of the Hexa and Herb 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.