Misidentified Human Gene Functions with Mouse Models: The Case of the Retinoblastoma Gene Family in Senescence

Show simplified metadata
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.creatorAlessio, N
dc.creatorCapasso, S
dc.creatorFerone, A
dc.creatorDi Bernardo, G
dc.creatorCipollaro, M
dc.creatorCasale, F
dc.creatorPeluso, G
dc.creatorGiordano, A
dc.creatorGalderisi, U
dc.creator.orcidGiordano, Antonio|0000-0002-5959-016X
dc.date.accessioned2021-01-22T15:20:56Z
dc.date.available2021-01-22T15:20:56Z
dc.date.issued2017-10-01
dc.date.updated2021-01-22T15:20:52Z
dc.description.abstract© 2017 The Authors Although mice models rank among the most widely used tools for understanding human genetics, biology, and diseases, differences between orthologous genes among species as close as mammals are possible, particularly in orthologous gene pairs in which one or more paralogous (i.e., duplicated) genes appear in the genomes of the species. Duplicated genes can possess overlapping functions and compensate for each other. The retinoblastoma gene family demonstrates typical composite functionality in its three member genes (i.e., RB1, RB2/P130, and P107), all of which participate in controlling the cell cycle and associated phenomena, including proliferation, quiescence, apoptosis, senescence, and cell differentiation. We analyzed the role of the retinoblastoma gene family in regulating senescence in mice and humans. Silencing experiments with each member of the gene family in mesenchymal stromal cells (MSCs) and fibroblasts from mouse and human tissues demonstrated that RB1 may be indispensable for senescence in mouse cells, but not in human ones, as an example of species specificity. Furthermore, although RB2/P130 seems to be implicated in maintaining human cell senescence, the function of RB1 within any given species might differ by cell type, as an example of cell specificity. For instance, silencing RB1 in mouse fibroblasts induced a reduced senescence not observed in mouse MSCs. Our findings could be useful as a general paradigm of cautions to take when inferring the role of human genes analyzed in animal studies and when examining the role of the retinoblastoma gene family in detail.
dc.format.extent781-790
dc.identifier.doihttp://dx.doi.org/10.34944/dspace/4857
dc.identifier.issn1522-8002
dc.identifier.issn1476-5586
dc.identifier.other28865301 (pubmed)
dc.identifier.urihttp://hdl.handle.net/20.500.12613/4875
dc.language.isoen
dc.relation.doi10.1016/j.neo.2017.06.005
dc.relation.haspartNeoplasia (United States)
dc.relation.isreferencedbyElsevier BV
dc.rightsCC BY-NC-ND
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAnimals
dc.subjectCells, Cultured
dc.subjectCellular Senescence
dc.subjectDisease Models, Animal
dc.subjectFibroblasts
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectGene Silencing
dc.subjectGenetic Association Studies
dc.subjectHumans
dc.subjectMesenchymal Stem Cells
dc.subjectMice
dc.subjectMice, Knockout
dc.subjectMultigene Family
dc.subjectRNA Processing, Post-Transcriptional
dc.subjectRNA, Small Interfering
dc.subjectRetinoblastoma Protein
dc.subjectSignal Transduction
dc.subjectTranscription, Genetic
dc.titleMisidentified Human Gene Functions with Mouse Models: The Case of the Retinoblastoma Gene Family in Senescence
dc.typeArticle
dc.type.genreJournal Article
refterms.dateFOA2021-01-22T15:20:57Z
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Misidentified Human Gene Functions with Mouse Models The Case of the Retinoblastoma Gene Family in Senescence.pdf
Size:
1.52 MB
Format:
Adobe Portable Document Format
Download
Collections
Faculty/Researcher Works