Pex13 inactivation in the mouse disrupts peroxisome biogenesis and leads to a Zellweger syndrome phenotype

Maxwell, Megan, Bjorkman, Jonas, Nguyen, Tam, Sharp, Peter, Finnie, John, Paterson, Carol, Tonks, Ian, Paton, Barbara C., Kay, Graham F. and Crane, Denis I. (2003) Pex13 inactivation in the mouse disrupts peroxisome biogenesis and leads to a Zellweger syndrome phenotype. Molecular and Cellular Biology, 23 16: 5947-5957. doi:10.1128/MCB.23.16.5947-5957.2003

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Author Maxwell, Megan
Bjorkman, Jonas
Nguyen, Tam
Sharp, Peter
Finnie, John
Paterson, Carol
Tonks, Ian
Paton, Barbara C.
Kay, Graham F.
Crane, Denis I.
Title Pex13 inactivation in the mouse disrupts peroxisome biogenesis and leads to a Zellweger syndrome phenotype
Journal name Molecular and Cellular Biology   Check publisher's open access policy
ISSN 0270-7306
Publication date 2003-08
Sub-type Article (original research)
DOI 10.1128/MCB.23.16.5947-5957.2003
Open Access Status File (Publisher version)
Volume 23
Issue 16
Start page 5947
End page 5957
Total pages 11
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
Abstract Zellweger syndrome is the archetypical peroxisome biogenesis disorder and is characterized by defective import of proteins into the peroxisome, leading to peroxisomal metabolic dysfunction and widespread tissue pathology. In humans, mutations in the PEX13 gene, which encodes a peroxisomal membrane protein necessary for peroxisomal protein import, can lead to a Zellweger phenotype. To develop mouse models for this disorder, we have generated a targeted mouse with a loxP-modified Pex13 gene to enable conditional Cre recombinase-mediated inactivation of Pex13. In the studies reported here, we crossed these mice with transgenic mice that express Cre recombinase in all cells to generate progeny with ubiquitous disruption of Pex13. The mutant pups exhibited many of the clinical features of Zellweger syndrome patients, including intrauterine growth retardation, severe hypotonia, failure to feed, and neonatal death. These animals lacked morphologically intact peroxisomes and showed deficient import of matrix proteins containing either type 1 or type 2 targeting signals. Biochemical analyses of tissue and cultured skin fibroblasts from these animals indicated severe impairment of peroxisomal fatty acid oxidation and plasmalogen synthesis. The brains of these animals showed disordered lamination in the cerebral cortex, consistent with a neuronal migration defect. Thus, Pex13-/- mice reproduce many of the features of Zellweger syndrome and PEX13 deficiency in humans. Copyright © 2003, American Society for Microbiology.
Keyword Zellweger syndrome
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
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