Nature Genetics
17, 49 - 57 (1997)
doi:10.1038/ng0997-49
A mouse model for Zellweger syndromeMyriam Baes1, 6, Pierre Gressens2, Eveline Baumgart3, Peter Carmeliet4, Minne Casteels5, Marc Fransen5, Philippe Evrard2, Dariush Fahimi3, Peter E. Declercq1, Désiré Collen4, Paul P. van Veldhoven5
& Guy P. Mannaerts5
1Laboratory of Clinical Chemistry, Katholieke Universiteit Leuven, Leuven, Belgium.
2Service de Neurologic Pédiatrique et Laboratoire de Neurologie du Développement, HôpitalRobert-Debré, Paris, France.
3Institut für Anatomie und Zellbiologie II, Universität Heidelberg, Heidelberg, Germany.
4Center for Transgene Technology and Gene Therapy, Vlaams Instituut voor Biotechnologie, Leuven, Belgium.
5Laboratory of Pharmacology, Katholieke Universiteit Leuven, Leuven, Belgium.
6e-mail: myriam.baes@uz.kuleuven.ac.be. 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.
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