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Remarkable composition shift of cone subtypes combined with changes on phototransduction due to cone mosaicism induced by ARR3 variants

ABSTRACT: Heterozygous variants in ARR3, encoding cone arrestin, have been identified to cause high myopia with a unique X-linked female limited inheritance but the potential mechanism for the unusual anti-X-linked pattern is still unclear. Arr3 expression profiles showed that Arr3, with significant expression in retina since P14, was almost co-stained with Opsin red/green in cones including some partially co-stained with both Opsin red/green and Opsin blue. And then Arr3 knock-in mice and Arr3 knock-out rats were generated. A mosaic expression of Arr3 was present in rodents with Arr3 heterozygous deficiency according to retinal flat-mount staining. Retinal single-cell RNA sequencing revealed significant changes in proportion of three cone sub-clusters in Arr3+/- rats, namely significantly decreased M/S cones, and significantly increased S cones. Pde6h was the only one differentially expressed genes (DEGs) shred in M/S cones in the comparison group Arr3+/+ vs. Arr3+/- and Arr3-/0 vs. Arr3+/-, but not in Arr3+/+ vs. Arr3-/0. These results suggest that heterozygous Arr3 loss in cones causes mosaic changes of cone subtypes that might mimic defocus visual signals in phototransduction.

ORGANISM(S): Rattus

PROVIDER: GSE309092 | GEO | 2025/12/31

REPOSITORIES: GEO

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Remarkable composition shift of cone subtypes combined with changes on phototransduction due to cone mosaicism induced by ARR3 variants

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