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Misidentified Human Gene Functions with Mouse Models: The Case of the Retinoblastoma Gene Family in Senescence
Open accessAbstract
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.
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Silencing of the RB gene induced senescence of human mesenchymal stromal cells (MSCs), but not of human fibroblasts, mouse MSCs, and mouse fibroblasts.
“Alessio et al. reported that silencing of RB gene induced senescence of human mesenchymal stromal cells (MSCs), but not of human fibroblasts, mouse MSCs, and mouse fibroblasts.”
From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [46]
RB might play different roles in senescence induction depending on cell types and species.
“The results indicate that RB might play different roles in senescence induction depending on cell types and species [46].”
From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [46]
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References 28 · Cited by 42
Research works printed but not linked: 24
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Metadata
- Authors
- Alessio, N., Capasso, S., Ferone, A., Di Bernardo, G., Cipollaro, M., Casale, F., Peluso, G., Giordano, A., & Galderisi, U.
- Affiliations
- University of Campania "Luigi Vanvitelli" (IT)
- National Research Council (IT)
- University of Siena (IT)
- Corresponding author
- Galderisi, Umberto
- ORCID
- Venue
- Neoplasia
- Publisher
- Elsevier BV
- Published
- 2017-10
- Volume
- 19
- Issue
- 10
- Pages
- 781-790
- ISSN
- 1476-5586 (ISSN-L)
- PMC
- PMC5577395
- OpenAlex
- W2753746371
- Cited by
- 42
- References
- 28
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 10 · 2023: 4 · 2022: 4 · 2021: 5 · 2020: 7 · 2019: 5 · 2018: 5
- FWCI
- 3.44
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Neoplasia (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
- TUScholarShare (Temple University) (submittedVersion, cc-by-nc-nd)
- Use Siena air (University of Siena) (submittedVersion)
- Funders
- Università degli Studi di Napoli Federico II
- Seconda Università degli Studi di Napoli
- Associazione Italiana per la Ricerca sul Cancro (IG 2014-15690, IG-2014)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- RB1, Rb2/p130, p107, cellular senescence, species specificity, orthologs, gene duplication, paralogs, mesenchymal stem cells, fibroblasts, gene silencing, human-mouse comparison, cell type specificity
- MeSH terms
- Animals, Cells, Cultured, Disease Models, Animal, Fibroblasts, Multigene Family, Humans, RNA Processing, Post-Transcriptional, Transcription, Genetic, Signal Transduction, Gene Expression Regulation, Neoplastic, Retinoblastoma Protein, Cellular Senescence, Mice, Knockout, Gene Silencing, RNA, Small Interfering, Mice, Genetic Association Studies, Mesenchymal Stem Cells
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