A MOUSE MODEL FOR ZELLWEGER-SYNDROME

The cerebro-hepato-renal syndrome of Zellweger is a fatal inherited di sease caused by deficient import of peroxisomal matrix proteins. The p athogenic mechanisms leading to extreme hypotonia, severe mental retar dation and early death are unknown. We generated a Zellweger animal mo del through inactivation of the murine Pxr1 gene (formally known as Pe x5) that encodes the import receptor for most peroxisomal matrix prote ins. Pxr1(-/-) mice lacked morphologically identifiable peroxisomes an d exhibited the typical biochemical abnormalities of Zellweger patient s. They displayed intrauterine growth retardation, were severely hypot onic at birth and died within 72 hours. Analysis of the neocortex reve aled impaired neuronal migration and maturation and extensive apoptoti c death of neurons.