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Retinal Degeneration Caused by Rod-Specific Dhdds Ablation Occurs without Concomitant Inhibition of ProteinN-Glycosylation

Rao Ramachandra, Sriganesh and Skelton, Lara A. and Wu, Fuguo and Onyśk, Agnieszka and Spolnik, Grzegorz and Danikiewicz, Witold and Butler, Mark C. and Stacks, Delores A. and Surmacz, Liliana and Mu, Xiuqian and Swiezewska, Ewa and Pittler, Steven J. and Fliesler, Steven J. (2020) Retinal Degeneration Caused by Rod-Specific Dhdds Ablation Occurs without Concomitant Inhibition of ProteinN-Glycosylation. iScience, 23 (6). p. 101198. ISSN 2589-0042

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Official URL: https://www.sciencedirect.com/science/article/pii/...


Dehydrodolichyl diphosphate synthase (DHDDS) catalyzes the committed step indolichol synthesis. Recessive mutations inDHDDScause retinitis pigmentosa(RP59), resulting in blindness. We hypothesized that rod photoreceptor-specificablation ofDhddswould cause retinal degeneration due to diminished dolichol-dependent proteinN-glycosylation.Dhddsflx/flxmice were crossed with rod-spe-cific Cre recombinase-expressing (Rho-iCre75) mice to generate rod-specificDhddsknockout mice (Dhddsflx/flxiCre+).In vivomorphological and electrophys-iological evaluation ofDhddsflx/flxiCre+retinas revealed mild retinal dysfunctionat postnatal (PN) 4 weeks, compared with age-matched controls; however, rapidphotoreceptor degeneration ensued, resulting in almost complete loss of rodsand cones by PN 6 weeks. Retina dolichol levels were markedly decreased byPN 4 weeks inDhddsflx/flxiCre+mice, relative to controls; despite this,N-glycosyl-ation of retinal proteins, including opsin (the dominant rod-specific glycoprotein),persisted inDhddsflx/flxiCre+mice. These findings challenge the conventionalmechanistic view of RP59 as a congenital disorder of glycosylation.

Item Type:Article
Subjects:Q Science > Q Science (General)
Q Science > QL Zoology
Divisions:Department of Lipid Biochemistry
ID Code:1889
Deposited By: dr Liliana Surmacz
Deposited On:17 Jun 2020 12:46
Last Modified:29 Jan 2021 10:21

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