title: Ablation of Chop Transiently Enhances Photoreceptor Survival but Does Not Prevent Retinal Degeneration in Transgenic Mice Expressing Human P23H Rhodopsin.
abstract: RHO (Rod opsin) encodes a G-protein coupled receptor that is expressed exclusively by rod photoreceptors of the retina and forms the essential photopigment, rhodopsin, when coupled with 11-cis-retinal. Many rod opsin disease -mutations cause rod opsin protein misfolding and trigger endoplasmic reticulum (ER) stress, leading to activation of the Unfolded Protein Response (UPR) signal transduction network. Chop is a transcriptional activator that is induced by ER stress and promotes cell death in response to chronic ER stress. Here, we examined the role of Chop in transgenic mice expressing human P23H rhodopsin (hP23H Rho Tg) that undergo retinal degeneration. With the exception of one time point, we found no significant induction of Chop in these animals and no significant change in retinal degeneration by histology and electrophysiology when hP23H Rho Tg animals were bred into a Chop (-/-) background. Our results indicate that Chop does not play a significant causal role during retinal degeneration in these animals. We suggest that other modules of the ER stress-induced UPR signaling network may be involved photoreceptor disease induced by P23H rhodopsin.
authors.affiliation: Department of Pathology, University of California, La Jolla, 92093, San Diego, CA, USA. wcchiang@ucsd.edu.
authors.forename: Wei-Chieh
authors.initials: WC
authors.lastname: Chiang
authors.affiliation: Department of Pathology, University of California, La Jolla, 92093, San Diego, CA, USA. vtj2101@gmail.com.
authors.forename: Victory
authors.initials: V
authors.lastname: Joseph
authors.affiliation: Department of Ophthalmology, University of California, 94143, San Francisco, CA, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Yasumura
authors.affiliation: Department of Ophthalmology, University of California, 94143, San Francisco, CA, USA. Michael.Matthes@ucsf.edu.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Matthes
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida, 32610, Gainesville, FL, USA. lewin@UFL.EDU.
authors.forename: Alfred S
authors.initials: AS
authors.lastname: Lewin
authors.affiliation: Department of Vision Sciences, University of Alabama at Birmingham, 35294, Birmingham, AL, USA. mgortk@uab.edu.
authors.forename: Marina S
authors.initials: MS
authors.lastname: Gorbatyuk
authors.affiliation: Department of Ophthalmology, University of California, 94143, San Francisco, CA, USA. kcahern@gmail.com.
authors.forename: Kelly
authors.initials: K
authors.lastname: Ahern
authors.affiliation: Departments of Anatomy and Ophthalmology, University of California, 94143, San Francisco, CA, USA. Matthew.LaVail@ucsf.edu.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: LaVail
authors.affiliation: Department of Pathology, University of California, La Jolla, 92093, San Diego, CA, USA. JLIN@ucsd.edu.|VA San Diego Healthcare System, 92161, San Diego, CA, USA. JLIN@ucsd.edu.
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Lin
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000235:genetics; D004596:Electroretinography; D015870:Gene Expression; D006801:Humans; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012243:Rhodopsin / Q000235:genetics* / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000172:deficiency / Q000235:genetics*; D019076:Transgenes / Q000235:genetics
chemical_list: C497250:Ddit3 protein, mouse; D051742:Transcription Factor CHOP; D012243:Rhodopsin
keywords: Chop; ER stress; P23H; Photoreceptor cell death; Retinal degeneration; Rhodopsin; Transgenic mice; UPR; Unfolded protein response