Photoreceptor Proliferation and Dysregulation of Cell Cycle Genes in Early Onset Inherited Retinal Degenerations

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dc.contributor.authorAguirre, Gustavo D
dc.contributor.authorGardiner, Kristin L
dc.contributor.authorAguirre, Gustavo D
dc.contributor.authorDowns, Louise
dc.contributor.authorGenini, Sem
dc.contributor.authorSantana, Evelyn
dc.contributor.authorGenini, Sem
dc.date2023-05-17T19:51:52.000
dc.date.accessioned2023-05-23T04:44:51Z
dc.date.available2023-05-23T04:44:51Z
dc.date.issued2016-03-11
dc.date.submitted2018-04-10T06:59:30-07:00
dc.description.abstractBackground Mitotic terminally differentiated photoreceptors (PRs) are observed in early retinal degeneration (erd), an inherited canine retinal disease driven by mutations in the NDR kinase STK38L (NDR2). Results We demonstrate that a similar proliferative response, but of lower magnitude, occurs in two other early onset disease models, X-linked progressive retinal atrophy 2 (xlpra2) and rod cone dysplasia 1 (rcd1). Proliferating cells are rod PRs, and not microglia or Müller cells. Expression of the cell cycle related genes RB1 and E2F1 as well as CDK2,4,6 was up-regulated, but changes were mutation-specific. Changes in cyclin expression differed across all genes, diseases and time points analyzed, although CCNA1 and CCNE1 expression increased with age in the three models suggesting that there is a dysregulation of cell cycle gene expression in all three diseases. Unique to erd, however, are mutation-specific changes in the expression of NDR kinases and Hippo signaling members with increased expression of MOB1and LATS1 in the newly generated hybrid rod/S-cones. Conclusions Our data raise the intriguing possibility that terminally differentiated normal PRs are kept from dividing by NDR2-MOB1 interaction. Furthermore, they provide the framework for the selection of candidate genes for further investigation as potential targets of therapy.
dc.identifier.urihttps://repository.upenn.edu/handle/20.500.14332/48915
dc.legacy.articleid1158
dc.legacy.fields10.1186/s12864-016-2477-9
dc.legacy.fulltexturlhttps://repository.upenn.edu/cgi/viewcontent.cgi?article=1158&context=vet_papers&unstamped=1
dc.rights<p>© 2016 Gardiner et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.</p>
dc.source.issue152
dc.source.issue221
dc.source.journalDepartmental Papers (Vet)
dc.source.journaltitleBMC Genomics
dc.source.peerreviewedtrue
dc.source.statuspublished
dc.source.volume17
dc.subject.otherCanine models
dc.subject.othercell cycle
dc.subject.othererd
dc.subject.otherhippo pathway
dc.subject.otherphotoreceptor degeneration
dc.subject.otherphotoreceptor mitosis
dc.subject.otherrcd1
dc.subject.otherxlpra2
dc.subject.otherMedicine and Health Sciences
dc.subject.otherVeterinary Medicine
dc.titlePhotoreceptor Proliferation and Dysregulation of Cell Cycle Genes in Early Onset Inherited Retinal Degenerations
dc.typeArticle
digcom.contributor.authorGardiner, Kristin L
digcom.contributor.authorDowns, Louise
digcom.contributor.authorBerta-Antalics, Agnes I
digcom.contributor.authorSantana, Evelyn
digcom.contributor.authorisAuthorOfPublication|email:gda@vet.upenn.edu|institution:University of Pennsylvania|Aguirre, Gustavo D
digcom.contributor.authorisAuthorOfPublication|email:geninis@vet.upenn.edu|institution:University of Pennsylvania|Genini, Sem
digcom.identifiervet_papers/152
digcom.identifier.contextkey11936302
digcom.identifier.submissionpathvet_papers/152
digcom.typearticle
dspace.entity.typePublication
person.identifier.orcid0000-0002-5228-256X
person.identifier.orcid0000-0002-5228-256X
relation.isAuthorOfPublication1a18ef39-6294-4816-a00d-fe4b64c3295a
relation.isAuthorOfPublication1a18ef39-6294-4816-a00d-fe4b64c3295a
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relation.isAuthorOfPublication.latestForDiscovery1a18ef39-6294-4816-a00d-fe4b64c3295a
upenn.schoolDepartmentCenterDepartmental Papers (Vet)
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