title: The neuronal migration defect in mice with Zellweger syndrome (Pex5 knockout) is not caused by the inactivity of peroxisomal beta-oxidation.
abstract: The purpose of this study was to investigate whether deficient peroxisomal beta-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 beta-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 MFP1/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 beta-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.
authors.affiliation: Laboratory of Clinical Chemistry, Faculty of Pharmaceutical Sciences, KU Leuven, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Baes
authors.forename: P
authors.initials: P
authors.lastname: Gressens
authors.forename: S
authors.initials: S
authors.lastname: Huyghe
authors.forename: Nys K
authors.initials: NK
authors.lastname: De
authors.forename: C
authors.initials: C
authors.lastname: Qi
authors.forename: Y
authors.initials: Y
authors.lastname: Jia
authors.forename: G P
authors.initials: GP
authors.lastname: Mannaerts
authors.forename: P
authors.initials: P
authors.lastname: Evrard
authors.forename: Veldhoven P P
authors.initials: VP
authors.lastname: Van
authors.forename: P E
authors.initials: PE
authors.lastname: Declercq
authors.forename: J K
authors.initials: JK
authors.lastname: Reddy
mesh_terms: D000818:Animals; D001923:Brain Chemistry; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D010084:Oxidation-Reduction; D000074435:Peroxisome-Targeting Signal 1 Receptor; D020675:Peroxisomes / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D015211:Zellweger Syndrome / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology
chemical_list: D005227:Fatty Acids; D000074435:Peroxisome-Targeting Signal 1 Receptor; C000614265:Pex5 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear