The neuronal migration defect in mice with Zellweger syndrome (Pex5 knockout) is not caused by the inactivity of peroxisomal β-oxidation

Myriam Baes*, P. Gressens, S. Huyghe, K. De Nys, C. Qi, Y. Jia, G. P. Mannaerts, P. Evrard, P. P. Van Veldhoven, P. E. Declercq, J. K. Reddy

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

The purpose of this study was to investigate whether deficient peroxisomal β-oxidation is causally involved in the neuronal migration defect observed in Pex5 knockout mice. These mice are models for Zellweger syndrome, a peroxisome biogenesis disorder. Neocortical development was evaluated in mice carrying a partial or complete defect of peroxisomal β-oxidation at the level of the second enzyme of the pathway, namely, the hydratase-dehydrogenase multifunctional/bifunctional enzymes MFP1/L-PBE and MFP2/D-PBE. In contrast to patients with multifunctional protein 2 deficiency who present with neocortical dysgenesis, impairment of neuronal migration was not observed in the single MFP2 or in the double MFPI/MFP2 knockout mice. At birth, the double knockout pups displayed variable growth retardation and about one half of them were severely hypotonic, whereas the single MFP2 knockout animals were all normal in the perinatal period. These results indicate that in the mouse, defective peroxisomal β-oxidation does not cause neuronal migration defects by itself. This does not exclude that the inactivity of this metabolic pathway contributes to the brain pathology in mice and patients with complete absence of functional peroxisomes.

Original languageEnglish (US)
Pages (from-to)368-374
Number of pages7
JournalJournal of neuropathology and experimental neurology
Volume61
Issue number4
DOIs
StatePublished - 2002

Keywords

  • Hypotonia
  • Multifunctional protein
  • Neuronal migration
  • Peroxisome
  • Very long chain fatty acid
  • Zellweger syndrome
  • β-Oxidation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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