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Residual rod function in CNGB1 mutant dogs

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Abstract

Purpose

Mutations in the cyclic nucleotide-gated (CNG) channel beta subunit (CNGB1) are an important cause of recessive retinitis pigmentosa. We identified a large animal model with a truncating mutation of CNGB1. This study reports the persistence of small, desensitized rod ERG responses in this model.

Methods

Dark-, light-adapted and chromatic ERGs were recorded in CNGB1 mutant dogs and age and breed matched controls. Comparisons were made with a dog model known to completely lack rod function; young dogs with a mutation in the rod phosphodiesterase 6 alpha subunit (PDE6A−/−). Immunohistochemistry (IHC) to label the rod CNG alpha (CNGA1) and CNGB1 subunits was performed.

Results

The dark-adapted ERG of CNGB1 mutant dogs had a raised response threshold with lack of normal rod response and a remaining cone response. Increasing stimulus strength resulted in the appearance of a separate, slower positive waveform following the dark-adapted cone b-wave. With increasing stimulus strength this increased in amplitude and became faster to merge with the initial b-wave. Comparison of responses from PDE6A−/− (cone only dogs) with CNGB1 mutant dogs to red and blue flashes and between dark-adapted and light-adapted responses supported the hypothesis that the CNGB1 mutant dog had residual desensitized rod responses. CNGB1 mutant dogs had a small amount of CNGA1 detectable in the outer segments.

Conclusions

CNGB1 mutant dogs have a residual ERG response from desensitized rods. This may be due to low levels of CNGA1 in outer segments.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

Not applicable.

Funding

SMPJ: NIH R24EY027285, Myers-Dunlap Endowment (SMPJ is the Myers-Dunlap Endowed Chair in Canine Health).

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Authors

Contributions

SMPJ conceived the project and coordinated project design and writing and editing the manuscript. NP participated in analysis of the data, writing and editing the manuscript. LMO participated in project design and data analysis and editing of the manuscript. JRQ performed the ERG recordings. PAW participated in project design and data analysis and immunohistochemistry. All have approved the submitted version.

Corresponding author

Correspondence to Simon M. Petersen-Jones.

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The authors declare that they have no conflicts of interest.

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This article does not contain any studies with human participants performed by any of the authors.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Petersen-Jones, S.M., Pasmanter, N., Occelli, L.M. et al. Residual rod function in CNGB1 mutant dogs. Doc Ophthalmol 145, 237–246 (2022). https://doi.org/10.1007/s10633-022-09899-3

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  • DOI: https://doi.org/10.1007/s10633-022-09899-3

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