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Retinal Impairments in Mice Lacking Both Nxnl1 and Nxnl2 Genes
Zheng Li1, Imen Harichane1, Thérèse Cronin2
1Department of Genetics, Sorbonne Université, CNRS, INSERM, Institut de la Vision, Paris, France.
Investigative Ophthalmology & Visual Science
|December 12, 2025
Summary
Simultaneous disruption of Nxnl1 and Nxnl2 genes in mice leads to severe retinal deficits, indicating these genes have complementary roles in photoreceptor health. This suggests combined Nxnl gene products could offer more effective retinitis pigmentosa therapies.
Area of Science:
- Ophthalmology
- Genetics
- Molecular Biology
Background:
- Nucleoredoxin-like 1 (Nxnl1) and Nxnl2 proteins, including rod-derived viability factor (RdCVF), show potential for treating retinitis pigmentosa (RP).
- Nxnl1 and Nxnl2 encode isoforms that support photoreceptor survival and mitigate oxidative stress, crucial for retinal health.
Purpose of the Study:
- To investigate the impact of combined Nxnl1 and Nxnl2 gene disruption on retinal structure and function.
- To compare the severity of retinal phenotypes in double knockout mice versus single knockout mice.
Main Methods:
- Generation of double Nxnl1-/-Nxnl2-/- knockout mice.
- Phenotypic analysis using spectral-domain optical coherence tomography (SD-OCT), fundus imaging, electroretinography (ERG), and immunofluorescence.
Main Results:
- Nxnl1-/-Nxnl2-/- mice exhibited significant outer nuclear layer thinning and rod dysfunction across all tested ages.
- Cone photoreceptor density was notably reduced in double knockout mice by 12.5 months.
- Impairments in both rod and cone photoreceptors were confirmed via retinal immunostaining.
Conclusions:
- Nxnl1 and Nxnl2 play non-redundant or complementary roles in maintaining photoreceptor integrity.
- The combined products of Nxnl genes present a promising avenue for developing more potent RP therapies.
