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dc.contributor.authorMaxwell, Megan
dc.contributor.authorBjorkman, Jonas
dc.contributor.authorNguyen, Tam
dc.contributor.authorSharp, Peter
dc.contributor.authorFinnie, John
dc.contributor.authorPaterson, Carol
dc.contributor.authorTonks, Ian
dc.contributor.authorC. Paton, Barbara
dc.contributor.authorF. Kay, Graham
dc.contributor.authorCrane, Denis
dc.date.accessioned2017-09-06T23:37:52Z
dc.date.available2017-09-06T23:37:52Z
dc.date.issued2003
dc.date.modified2007-03-29T07:59:52Z
dc.identifier.issn02707306
dc.identifier.doi10.1128/MCB.23.16.5947-5957.2003
dc.identifier.urihttp://hdl.handle.net/10072/6280
dc.description.abstractZellweger 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.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Society for Microbiology
dc.publisher.placeUnited States
dc.relation.ispartofpagefrom5947
dc.relation.ispartofpageto5957
dc.relation.ispartofedition2003
dc.relation.ispartofissue16
dc.relation.ispartofjournalMolecular and Cellular Biology
dc.relation.ispartofvolume23
dc.subject.fieldofresearchBiological Sciences
dc.subject.fieldofresearchMedical and Health Sciences
dc.subject.fieldofresearchcode06
dc.subject.fieldofresearchcode11
dc.titlePex13 Inactivation in the Mouse Disrupts Peroxisome Biogenesis and Leads to a Zellweger Syndrome Phenotype
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dc.description.versionPublished
gro.facultyGriffith Sciences, School of Natural Sciences
gro.rights.copyright© 2003 American Society for Microbiology. The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.
gro.date.issued2003
gro.hasfulltextFull Text
gro.griffith.authorCrane, Denis I.
gro.griffith.authorBjorkman, Jonas C.
gro.griffith.authorMaxwell, Megan
gro.griffith.authorNguyen, Tam H.


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