Cited by 116Metabolism and Genetic DisordersGenetics and Neurodevelopmental DisordersLysosomal Storage Disorders Research

Impaired neuronal migration and endochondral ossification in Pex7 knockout mice: a model for rhizomelic chondrodysplasia punctata

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Brites, P.·2003·Human Molecular Genetics

Abstract

Rhizomelic chondrodysplasia punctata is a human autosomal recessive disorder characterized by skeletal, eye and brain abnormalities. The disorder is caused by mutations in the PEX7 gene, which encodes the receptor for a class of peroxisomal matrix enzymes. We describe the generation and characterization of a Pex7 mouse knockout (Pex7(-/-)). Pex7(-/-) mice are born severely hypotonic and have a growth impairment. Mortality in Pex7(-/-) mice is highest in the perinatal period although some Pex7(-/-) mice survived beyond 18 months. Biochemically Pex7(-/-) mice display the abnormalities related to a Pex7 deficiency, i.e. a severe depletion of plasmalogens, impaired alpha-oxidation of phytanic acid and impaired beta-oxidation of very-long-chain fatty acids. In the intermediate zone of the developing cerebral cortex Pex7(-/-) mice have an increase in neuronal density. In vivo neuronal birthdating revealed that Pex7(-/-) mice have a delay in neuronal migration. Analysis of bone ossification in newborn Pex7(-/-) mice revealed a defect in ossification of distal bone elements of the limbs as well as parts of the skull and vertebrae. These findings demonstrate that Pex7 knockout mice provide an important model to study the role of peroxisomal functioning in the pathogenesis of the human disorder.

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Crossref · 10.1093/hmg/ddg236

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Authors
Brites, P.
Affiliations
Amsterdam UMC Location University of Amsterdam (NL)
Corresponding author
Brites, P.
Venue
Human Molecular Genetics
Published
2003-07-15
Volume
12
Issue
18
Pages
2255-2267
ISSN
  • 0964-6906 (ISSN-L)
  • 1460-2083
OpenAlex
W2138708884
Cited by
116
References
88
Citations by year
2026: 3 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 7 · 2021: 5 · 2020: 4 · 2019: 6 · 2018: 6 · 2017: 6 · 2016: 1 · 2015: 8 · 2014: 10 · 2013: 6 · 2012: 4
FWCI
1.89
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Human Molecular Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • UvA-DARE (University of Amsterdam) (publishedVersion)
  • VU Research Portal (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Research Portal (King's College London) (submittedVersion, other-oa)
  • Pure Amsterdam UMC (submittedVersion)
Funders
Calouste Gulbenkian Foundation
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
Keywords
rhizomelic chondrodysplasia punctata, PEX7, peroxisomal disorders, peroxisome biogenesis, neuronal migration, endochondral ossification, very long chain fatty acid beta-oxidation, mouse model, skeletal dysplasia, growth retardation
MeSH terms
Peroxisomal Targeting Signal 2 Receptor, Acetyl-CoA C-Acetyltransferase, Animals, Animals, Newborn, Brain, Cell Movement, Cells, Cultured, Diet, Fibroblasts, Liver, Mutation, Neurons, Osteoblasts, Osteoclasts, Osteogenesis, Oxidation-Reduction, Phytanic Acid, Phytol, Plasmalogens, Time Factors, Receptors, Cytoplasmic and Nuclear, Mice, Knockout, Gene Targeting, Chondrodysplasia Punctata, Rhizomelic, Peroxisomes, Mice

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