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A mouse model for Zellweger syndrome

Nature Genetics volume 17, pages 49–57 (1997)Cite this article

Abstract

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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Authors and Affiliations

  1. Laboratory of Clinical Chemistry, Katholieke Universiteit Leuven, Leuven, Belgium

    Myriam Baes & Peter E. Declercq

  2. Service de Neurologic Pédiatrique et Laboratoire de Neurologie du Développement, HôpitalRobert-Debré, Paris, France

    Pierre Gressens & Philippe Evrard

  3. Institut für Anatomie und Zellbiologie II, Universität Heidelberg, Heidelberg, Germany

    Eveline Baumgart & Dariush Fahimi

  4. Center for Transgene Technology and Gene Therapy, Vlaams Instituut voor Biotechnologie, Leuven, Belgium

    Peter Carmeliet & Désiré Collen

  5. Laboratory of Pharmacology, Katholieke Universiteit Leuven, Leuven, Belgium

    Minne Casteels, Marc Fransen, Paul P. van Veldhoven & Guy P. Mannaerts

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  1. Myriam Baes
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Correspondence to Myriam Baes.

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Baes, M., Gressens, P., Baumgart, E. et al. A mouse model for Zellweger syndrome. Nat Genet 17, 49–57 (1997). https://doi.org/10.1038/ng0997-49

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