{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:30:45Z","timestamp":1791937845472,"version":"4.3.4"},"reference-count":64,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,11,29]],"date-time":"2019-11-29T00:00:00Z","timestamp":1574985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Mutations in peripherin 2 (\n                    <jats:italic>PRPH2<\/jats:italic>\n                    ) have been associated with retinitis pigmentosa (RP) and macular\/pattern dystrophies, but the origin of this phenotypic variability is unclear. The majority of Prph2 mutations are located in the large intradiscal loop (D2), a region that contains seven cysteines involved in intra\u2010 and intermolecular disulfide bonding and protein folding. A mutation at cysteine 213, which is engaged in an intramolecular disulfide bond, leads to butterfly\u2010shaped pattern dystrophy in humans, in sharp contrast to mutations in the adjacent cysteine at position 214 which result in RP. To help understand this unexpected phenotypic variability, we generated a knockin mouse line carrying the C213Y disease mutation. The mutant Prph2 protein lost the ability to oligomerize with rod outer segment membrane protein 1 (Rom1), but retained the ability to form homotetramers. C213Y heterozygotes had significantly decreased overall Prph2 levels as well as decreased rod and cone function. Critically, supplementation with extra wild\u2010type Prph2 protein elicited improvements in Prph2 protein levels and rod outer segment structure, but not functional rescue in rods or cones. These findings suggest that not all interruptions of D2 loop intramolecular disulfide bonding lead to haploinsufficiency\u2010related RP, but rather that more subtle changes can lead to mutant proteins stable enough to exert gain\u2010of\u2010function defects in rods and cones. This outcome highlights the difficulty in targeting Prph2\u2010associated gain\u2010of\u2010function disease and suggests that elimination of the mutant protein will be a pre\u2010requisite for any curative therapeutic strategy.\n                  <\/jats:p>","DOI":"10.1096\/fj.201901888r","type":"journal-article","created":{"date-parts":[[2019,11,29]],"date-time":"2019-11-29T08:21:56Z","timestamp":1575015716000},"page":"1211-1230","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Novel molecular mechanisms for Prph2\u2010associated pattern dystrophy"],"prefix":"10.1096","volume":"34","author":[{"given":"Dibyendu","family":"Chakraborty","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering University of Houston Houston TX USA"},{"name":"Department of Cell Biology University of Oklahoma Health Sciences Center Oklahoma City OK 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