Related Experiment Video
Updated: Jun 17, 2026
RNA Isolation from Mouse Ocular Lens Epithelium and Fiber Cell Bulk Masses
Published on: October 10, 2025
A Pex7 hypomorphic mouse model for plasmalogen deficiency affecting the lens and skeleton
Nancy Braverman1, Rui Zhang, Li Chen
1Department of Human Genetics and Pediatrics, Montreal Children's Hospital Research Institute, McGill University, Montreal, QC, Canada. nancy.braverman@mcgill.ca
Insights
Rhizomelic chondrodysplasia punctata type 1 (RCDP1) is a peroxisome disorder. A new mouse model with reduced PEX7 function shows mild RCDP1 features, enabling further study of plasmalogen deficiency.
Area of Science:
- Biochemistry
- Genetics
- Cell Biology
Background:
- Rhizomelic chondrodysplasia punctata type 1 (RCDP1) is a rare autosomal recessive peroxisome biogenesis disorder.
- RCDP1 is caused by defects in the PEX7 gene, leading to plasmalogen deficiency and phytanic acid accumulation.
- Current animal models exhibit severe phenotypes, limiting therapeutic research.
Purpose of the Study:
- To engineer a hypomorphic mouse model of RCDP1 with reduced PEX7 function.
- To investigate the biochemical and clinical manifestations of partial PEX7 deficiency.
- To establish a model for studying plasmalogen function and testing therapeutic interventions.
Main Methods:
- Generated a hypomorphic mouse model by reducing Pex7 transcript levels to <5% of wild type.
- Phenotypic analysis included growth, lifespan, cataract development, and skeletal ossification.
- Biochemical analyses measured plasmalogen levels, phytanic acid, and Pex7 ligand import.
Main Results:
- The Pex7 hypomorphic mice exhibited petite stature, early cataracts, delayed endochondral ossification, and lens fiber abnormalities.
- Biochemical hallmarks of RCDP1, including plasmalogen deficiency and phytanic acid accumulation, were observed.
- Dietary batyl alcohol supplementation restored ether phospholipids but did not ameliorate the phenotype.
Conclusions:
- This mouse model recapitulates key features of milder RCDP1, highlighting the skeleton and lens as sensitive indicators of plasmalogen deficiency.
- The model facilitates the study of plasmalogen roles in tissue function and the development of novel therapies for RCDP1.
- Further research can explore the specific functions of plasmalogens and test interventions in this relevant animal model.
Abstract:
Rhizomelic chondrodysplasia punctata type 1 is a peroxisome biogenesis disorder with the clinical features of rhizomelia, abnormal epiphyseal calcifications, congenital cataracts, and profound growth and developmental delays. It is a rare autosomal recessive disorder, caused by defects in the peroxisome receptor, PEX7. The pathology results from a deficiency of plasmalogens, a critical class of ether phospholipids whose functions are largely unknown. To study plasmalogens in an animal model, avoid early mortality and facilitate therapeutic investigations in this disease, we engineered a hypomorphic mouse model in which Pex7 transcript levels are reduced to less than 5% of wild type. These mice are born in expected ratios, are fertile and have a normal life span. However, they are petite and develop early cataracts. Further investigations showed delayed endochondral ossification and abnormalities in lens fibers. The biochemical features of reduced Pex7 function were reproduced in this model, including tissue plasmalogen deficiency, phytanic acid accumulation, reduced import of Pex7 ligands and consequent defects in plasmalogen biosynthesis and phytanic acid oxidation. Dietary supplementation with batyl alcohol, a plasmalogen precursor, recovered ether phospholipids in blood, but did not alter the clinical phenotype. The relatively mild phenotype of these mice mimics patients with milder PEX7 defects, and highlights the skeleton and lens as sensitive markers of plasmalogen deficiency. The role of plasmalogens in the normal function of these tissues at various ages can now be studied and additional therapeutic interventions tested in this model.
