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Molecular and Cellular Biology, June 2002, p. 4358-4365, Vol. 22, No. 12
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.12.4358-4365.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

PEX11ß Deficiency Is Lethal and Impairs Neuronal Migration but Does Not Abrogate Peroxisome Function

Xiaoling Li,1 Eveline Baumgart,1 James C. Morrell,1 Gerardo Jimenez-Sanchez,2 David Valle,2 and Stephen J. Gould1*

Department of Biological Chemistry,1 The Howard Hughes Medical Institute and Departments of Pediatrics and Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 212052

Received 23 January 2002/ Returned for modification 25 February 2002/ Accepted 5 March 2002

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 PEX11ß 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, PEX11ß 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 ß-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.

* Corresponding author. Mailing address: Department of Biological Chemistry, The Johns Hopkins University School of Medicine, 725 North Wolfe St., Baltimore, MD 21205. Phone: (410) 955-3424. Fax: (410) 955-0215. E-mail: sgould{at}jhmi.edu.

Molecular and Cellular Biology, June 2002, p. 4358-4365, Vol. 22, No. 12
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.12.4358-4365.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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