A Pex7 hypomorphic mouse model for plasmalogen deficiency affecting the lens and skeleton

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.