TARGETED DISRUPTION OF THE HEXA GENE RESULTS IN MICE WITH BIOCHEMICAL AND PATHOLOGICAL FEATURES OF TAY-SACHS-DISEASE
TARGETED DISRUPTION OF THE HEXA GENE RESULTS IN MICE WITH BIOCHEMICAL AND PATHOLOGICAL FEATURES OF TAY-SACHS-DISEASE
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DOI：
10.1073/pnas.91.21.9975
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发表时间：
1994-10-11
影响因子：
11.1
通讯作者：
PROIA, RL
中科院分区：
文献类型：
--
作者：
YAMANAKA, S;JOHNSON, MD;PROIA, RL
泰-萨二氏病是G（M2）神经节苷脂沉积症的原型，是婴儿期的一种灾难性神经退行性疾病。该疾病是由HEXA基因突变引起的，导致溶酶体酶β-氨基己糖苷酶A缺失。由于酶缺乏，G（M2）神经节苷脂逐渐积累，从胎儿早期开始，在中枢神经系统中过量。从出生后第一年开始，精神和运动能力迅速恶化，导致2-4岁死亡。通过有针对性地破坏胚胎干细胞中的小鼠Hexa基因，我们已经产生了具有泰-萨二氏病的生化和神经病理学特征的小鼠。突变小鼠表现出
Tay-Sachs disease, the prototype of the G(M2) gangliosidoses, is a catastrophic neurodegenerative disorder of infancy. The disease is caused by mutations in the HEXA gene resulting in an absence of the lysosomal enzyme, beta-hexosaminidase A. As a consequence of the enzyme deficiency, G(M2) ganglioside accumulates progressively, beginning early in fetal life, to excessive amounts in the central nervous system. Rapid mental and motor deterioration starting in the first year of life leads to death by 2-4 years of age. Through the targeted disruption of the mouse Hexa gene in embryonic stem cells, we have produced mice with biochemical and neuropathologic features of Tay-Sachs disease. The mutant mice displayed