PEX11β deficiency is lethal and impairs neuronal migration but does not abrogate peroxisome function

Xiaoling Li, Eveline Baumgart, James C. Morrell, Gerardo Jimenez-Sanchez, David Valle, Stephen J. Gould

Research output: Contribution to journalArticlepeer-review

Abstract

Zellweger syndrome is a lethal neurological disorder characterized by severe defects in peroxisomal protein import. The resulting defects in peroxisome metabolism and the accumulation of peroxisomal substrates are thought to cause the other Zellweger syndrome phenotypes, including neuronal migration defects, hypotonia, a developmental delay, and neonatal lethality. These phenotypes are also manifested in mouse models of Zellweger syndrome generated by disruption of the PEX5 or PEX2 gene. Here we show that mice lacking peroxisomal membrane protein PEX11β display several pathologic features shared by these mouse models of Zellweger syndrome, including neuronal migration defects, enhanced neuronal apoptosis, a developmental delay, hypotonia, and neonatal lethality. However, PEX11β deficiency differs significantly from Zellweger syndrome and Zellweger syndrome mice in that it is not characterized by a detectable defect in peroxisomal protein import and displays only mild defects in peroxisomal fatty acid β-oxidation and peroxisomal ether lipid biosynthesis. These results demonstrate that the neurological pathologic features of Zellweger syndrome can occur without peroxisomal enzyme mislocalization and challenge current models of Zellweger syndrome pathogenesis.

Original languageEnglish (US)
Pages (from-to)4358-4365
Number of pages8
JournalMolecular and cellular biology
Volume22
Issue number12
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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