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• W3110104568 abstract "Mutations in prominin-1 (prom1) and photoreceptor cadherin (cdhr1) are associated with inherited retinal degenerative disorders but their functions remain unknown. Here, we used CRISPR-Cas9 to generate prom1-null, cdhr1-null, and prom1 plus cdhr1 double-null Xenopuslaevis and then documented the effects of these mutations on photoreceptor structure and function. Prom1-null mutations resulted in severely dysmorphic photoreceptors comprising overgrown and disorganized disc membranes. Cone outer segments were more severely affected than rods and had an impaired electroretinogram response. Cdhr1-null photoreceptors did not appear grossly dysmorphic, but ultrastructural analysis revealed that some disc membranes were overgrown or oriented vertically within the plasma membrane. Double-null mutants did not differ significantly from prom1-null mutants. Our results indicate that neither prom1 nor cdhr1 are necessary for outer segment disc membrane evagination or the fusion event that controls disc sealing. Rather, they are necessary for the higher-order organization of the outer segment. Prom1 may align and reinforce interactions between nascent disc leading edges, a function more critical in cones for structural support. Cdhr1 may secure discs in a horizontal orientation prior to fusion and regulate cone lamellae size.This article has an associated First Person interview with the first author of the paper." @default.
• W3110104568 created "2020-12-07" @default.
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• W3110104568 date "2020-01-01" @default.
• W3110104568 modified "2023-09-25" @default.
• W3110104568 title "Distinct roles for prominin-1 and photoreceptor cadherin in outer segment disc morphogenesis in CRISPR-altered <i>X. laevis</i>" @default.
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• W3110104568 doi "https://doi.org/10.1242/jcs.253906" @default.
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