Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Vertebrate Animal Models of RP59: Current Status and Future Prospects

Steven J. Fliesler
* ORCID logo ,
Sriganesh Ramachandra Rao
ORCID logo ,
Mai N. Nguyen
,
Mahmoud Tawfik KhalafAllah
,
Steven J. Pittler
ORCID logo
Version 1 : Received: 14 September 2022 / Approved: 22 September 2022 / Online: 22 September 2022 (10:18:11 CEST)

A peer-reviewed article of this Preprint also exists.

Fliesler, S.J.; Ramachandra Rao, S.; Nguyen, M.N.; KhalafAllah, M.T.; Pittler, S.J. Vertebrate Animal Models of RP59: Current Status and Future Prospects. Int. J. Mol. Sci. 2022, 23, 13324. Fliesler, S.J.; Ramachandra Rao, S.; Nguyen, M.N.; KhalafAllah, M.T.; Pittler, S.J. Vertebrate Animal Models of RP59: Current Status and Future Prospects. Int. J. Mol. Sci. 2022, 23, 13324.

Abstract

Retinitis pigmentosa-59 (RP59) is a rare, recessive form of RP, caused by mutations in the gene encoding DHDDS (dehydrodolichyl diphosphate synthase). DHDDS forms a heterotetrameric complex with Nogo-B Receptor (NgBR; gene NUS1) to form a cis-prenyltransferase (CPT) enzyme complex, which is required for synthesis of dolichol, which in turn is required for protein N-glycosylation as well as other glycosylation reactions in eukaryotic cells. Herein, we review the published phenotypic characteristics of RP59 models extant, with an emphasis on their ocular phenotypes, based primarily upon knock-in of known RP59-associated DHDDS mutations as well as cell type- and tissue-specific knockout of DHDDS alleles in mice. We also briefly review findings in RP59 patients with retinal disease and other patients with DHDDS mutations causing epilepsy and other neurologic disease. We discuss these findings in the context of addressing “knowledge gaps” in our current understanding of the underlying pathobiology mechanism of RP59, as well as their potential utility for developing therapeutic interventions to block the onset, or to dampen the severity or progression, of RP59.

Keywords

cis-prenyltransferase; DHDDS; dolichol; Nogo-B receptor; retinal degeneration; RP59

Subject

Medicine and Pharmacology, Ophthalmology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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