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Updated: Jan 17, 2026
Mouse Eye Enucleation for Remote High-throughput Phenotyping
Published on: November 19, 2011
Identification of coexisting Mfrprd6 and Pde6brd10 mutations causing spontaneous retinal detachment in commercially
Asaka Lee Shiozawa1,2, Maika Hosoi Kobayashi1, Yusuke Shiozawa2
1Department of Ophthalmology, Nippon Medical School, Sendagi, Bunkyo-ku, Tokyo, Japan.
Purpose:
The rd6 mouse model, characterized by retinal degeneration due to an Mfrp mutation, has been widely studied. However, we identified a subset of rd6 mice that developed severe non-rhegmatogenous retinal detachment (rd6-RD), suggesting the presence of additional genetic factors. This study aimed to characterize the retinal phenotype of rd6-RD mice and identify potential causative genetic mutations.
Methods:
We performed optical coherence tomography, fundus imaging, electroretinography, and histological analysis to compare retinal structures and functions between rd6, rd6-RD, and C57BL/6J mice. Whole-genome sequencing was conducted to identify potential mutations associated with the retinal detachment phenotype.
Results:
Optical coherence tomography revealed retinal detachment in rd6-RD mice as early as 4 weeks old, with complete loss of the outer nuclear layer by 6 weeks. Fundus examination at 11 weeks showed pale fundi and narrowed, whitened retinal vessels in rd6-RD mice, distinct from rd6 mice. On electroretinography, rd6-RD mice displayed significantly diminished a- and b-wave amplitudes, with no detectable responses by 10 weeks. Histological analysis confirmed severe outer retinal degeneration and disappearance of the outer layers in rd6-RD mice. Whole-genome sequencing identified a missense R560C mutation in Pde6b, corresponding to the Pde6brd10 mutation, in rd6-RD mice.
Conclusions:
A subset of rd6 mice exhibited severe retinal detachment and outer retinal degeneration, distinct from the previously characterized Mfrp-related phenotype. The identification of the Pde6brd10 mutation suggests that these mice possess a dual-mutant genotype (Mfrprd6 and Pde6brd10), exacerbating retinal degeneration. These findings highlight the importance of genetic verification in commercially available mouse models and provide new insights into the genetic complexity of inherited retinal degenerations.
Insights
A subset of rd6 mice developed severe retinal detachment due to a dual mutation. This finding underscores the importance of genetic verification in mouse models for inherited retinal degeneration research.
Area of Science:
- Genetics
- Ophthalmology
- Molecular Biology
Background:
- The rd6 mouse model, caused by an Mfrp mutation, is used to study retinal degeneration.
- A subset of rd6 mice unexpectedly developed severe non-rhegmatogenous retinal detachment (rd6-RD).
- This suggests additional genetic factors contributing to the rd6 phenotype.
Purpose of the Study:
- To characterize the retinal phenotype of rd6-RD mice.
- To identify genetic mutations responsible for retinal detachment in rd6-RD mice.
Main Methods:
- Comparative analysis of rd6, rd6-RD, and C57BL/6J mice using optical coherence tomography, fundus imaging, electroretinography, and histology.
- Whole-genome sequencing to identify causative mutations.
Main Results:
- rd6-RD mice showed retinal detachment by 4 weeks and complete outer nuclear layer loss by 6 weeks.
- Distinct fundus findings in rd6-RD mice included pale fundi and narrowed, whitened retinal vessels.
- Electroretinography revealed diminished a- and b-wave amplitudes, with no responses by 10 weeks in rd6-RD mice.
- Whole-genome sequencing identified a Pde6brd10 mutation in rd6-RD mice.
Conclusions:
- A subset of rd6 mice exhibits a distinct phenotype of severe retinal detachment and degeneration.
- The Pde6brd10 mutation in rd6 mice indicates a dual-mutant genotype (Mfrprd6 and Pde6brd10), worsening retinal degeneration.
- Genetic verification of mouse models is crucial for accurate research on inherited retinal degenerations.
