A mouse model for Zellweger syndrome
A mouse model for Zellweger syndrome
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DOI：
10.1038/ng0997-49
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发表时间：
1997-09-01
期刊：
影响因子：
30.8
通讯作者：
Mannaerts, GP
中科院分区：
文献类型：
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作者：
Baes, M;Gressens, P;Mannaerts, GP
Zellweger脑-肝-肾综合征是一种致命的遗传性疾病，其原因是过氧体基质蛋白输入不足。导致极低眼压、严重智力低下和过早死亡的发病机制尚不清楚。我们通过灭活小鼠Pxr1基因(正式名称为Pex5)产生了Zellweger动物模型，Pxr1基因编码大多数过氧化体基质蛋白的输入受体。Pxr1(-/-)小鼠缺乏形态上可识别的过氧化物体，并表现出典型的齐薇格患者的生化异常。他们表现为宫内发育迟缓，出生时严重低眼压，并在72小时内死亡。对新皮质的分析显示，神经元的迁移和成熟受到损害，神经元出现广泛的凋亡死亡。
The cerebro-hepato-renal syndrome of Zellweger is a fatal inherited disease caused by deficient import of peroxisomal matrix proteins. The pathogenic mechanisms leading to extreme hypotonia, severe mental retardation and early death are unknown. We generated a Zellweger animal model through inactivation of the murine Pxr1 gene (formally known as Pex5) that encodes the import receptor for most peroxisomal matrix proteins. Pxr1(-/-) mice lacked morphologically identifiable peroxisomes and exhibited the typical biochemical abnormalities of Zellweger patients. They displayed intrauterine growth retardation, were severely hypotonic at birth and died within 72 hours. Analysis of the neocortex revealed impaired neuronal migration and maturation and extensive apoptotic death of neurons.