Impaired neuronal migration and endochondral ossification in Pex7 knockout mice: a model for rhizomelic chondrodysplasia punctata
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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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Bams-Mengerink, A. M., Koelman, J. H., Waterham, H., Barth, P. G., & Poll-The, B. T. (2013) · Orphanet Journal of Rare Diseases · doi:10.1186/1750-1172-8-174 · Cited by 59 · see citing works
Liegel, R., Chang, B., Dubielzig, R., & Sidjanin, D. J. (2011) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2011.02.002 · Cited by 38 · see citing works
Krysko, O., Bottelbergs, A., Veldhoven, P. V., & Baes, M. (2010) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2010.02.003 · Cited by 17 · see citing works
- Authors
- Brites, P.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Corresponding author
- Brites, P.
- ORCID
- Brites, P.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- 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
- green
- kclpure.kcl.ac.uk
- 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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