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

Alessio, N
; 
Capasso, S
; 
Ferone, A
; 
Di Bernardo, G
; 
Cipollaro, M
; 
Casale, F
; 
Peluso, G
; 
Giordano, A
; 
Galderisi, U
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Journal Article
Date
2017-10-01
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Subject
Animals
 Cells, Cultured
 Cellular Senescence
 Disease Models, Animal
 Fibroblasts
 Gene Expression Regulation, Neoplastic
 Gene Silencing
 Genetic Association Studies
 Humans
 Mesenchymal Stem Cells
 Mice
 Mice, Knockout
 Multigene Family
 RNA Processing, Post-Transcriptional
 RNA, Small Interfering
 Retinoblastoma Protein
 Signal Transduction
 Transcription, Genetic
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http://hdl.handle.net/20.500.12613/4875
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Misidentified Human Gene Functions with Mouse Models The Case of the Retinoblastoma Gene Family in Senescence.pdf
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DOI
10.1016/j.neo.2017.06.005
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.
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Elsevier BV
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Neoplasia (United States)
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