Baes M, Gressens P, Baumgart E, Carmeliet P, Casteels M, Fransen M, Evrard P, Fahimi D, Declercq P E, Collen D, van Veldhoven P P, Mannaerts G P
Laboratory of Clinical Chemistry, Kathlieke Universiteit Leuven, Belgium.
Nat Genet. 1997 Sep;17(1):49-57. doi: 10.1038/ng0997-49.
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.
泽尔韦格脑肝肾综合征是一种由过氧化物酶体基质蛋白导入缺陷引起的致命性遗传病。导致极度肌张力减退、严重智力发育迟缓及早期死亡的致病机制尚不清楚。我们通过使编码大多数过氧化物酶体基质蛋白导入受体的小鼠Pxr1基因（原称为Pex5）失活，构建了泽尔韦格动物模型。Pxr1基因敲除小鼠缺乏形态上可识别的过氧化物酶体，并表现出泽尔韦格患者典型的生化异常。它们出现宫内生长迟缓，出生时严重肌张力减退，并在72小时内死亡。对新皮层的分析显示神经元迁移和成熟受损以及神经元广泛凋亡死亡。
