Rb deficiency, neuronal survival and neurodegeneration: In search of the perfect mouse model
Three decades following the introduction of the first Rb knockout (KO) mouse model, the role of this critical protein in regulating brain development during embryogenesis and beyond remains a major scientific interest. Rb is a tumor suppressor gene known as the master regulator of the G1/S checkpoin...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Current Research in Neurobiology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2665945X23000025 |
| _version_ | 1797799947086594048 |
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| author | Saad Omais Yara E. El Atie Noël Ghanem |
| author_facet | Saad Omais Yara E. El Atie Noël Ghanem |
| author_sort | Saad Omais |
| collection | DOAJ |
| description | Three decades following the introduction of the first Rb knockout (KO) mouse model, the role of this critical protein in regulating brain development during embryogenesis and beyond remains a major scientific interest. Rb is a tumor suppressor gene known as the master regulator of the G1/S checkpoint and control of cell cycle progression in stem and progenitor cells, but also their differentiated progeny. Here, we review the recent literature about the various Rb conditional Knockout (cKO) and inducible Knockout (iKO) models studied thus far, highlighting how findings should always be interpreted in light of the model and context under inquiry especially when studying the role of Rb in neuronal survival. There is indeed evidence of age-specific, cell type-specific and region-specific effects following Rb KO in the embryonic and the adult mouse brain. In terms of modeling neurodegenerative processes in human diseases, we discuss cell cycle re-entry (CCE) as a candidate mechanism underlying the increased vulnerability of Rb-deficient neurons to cell death. Notably, mouse models may limit the extent to which CCE due to Rb inactivation can mimic the pathological course of these disorders, such as Alzheimer's disease. These remarks ought to be considered in future research when studying the consequences of Rb inactivation on neuronal generation and survival in rodents and their corresponding clinical significance in humans. |
| first_indexed | 2024-03-13T04:27:07Z |
| format | Article |
| id | doaj.art-9b8aa468a4ef441284c63261d8cdbc9c |
| institution | Directory Open Access Journal |
| issn | 2665-945X |
| language | English |
| last_indexed | 2024-03-13T04:27:07Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Neurobiology |
| spelling | doaj.art-9b8aa468a4ef441284c63261d8cdbc9c2023-06-20T04:20:44ZengElsevierCurrent Research in Neurobiology2665-945X2023-01-014100074Rb deficiency, neuronal survival and neurodegeneration: In search of the perfect mouse modelSaad Omais0Yara E. El Atie1Noël Ghanem2Department of Biology, American University of Beirut, LebanonDepartment of Biology, American University of Beirut, LebanonCorresponding author. Department of Biology, American University of Beirut, PO Box 11-0236, Riad El Solh, 1107 2020, Beirut, Lebanon.; Department of Biology, American University of Beirut, LebanonThree decades following the introduction of the first Rb knockout (KO) mouse model, the role of this critical protein in regulating brain development during embryogenesis and beyond remains a major scientific interest. Rb is a tumor suppressor gene known as the master regulator of the G1/S checkpoint and control of cell cycle progression in stem and progenitor cells, but also their differentiated progeny. Here, we review the recent literature about the various Rb conditional Knockout (cKO) and inducible Knockout (iKO) models studied thus far, highlighting how findings should always be interpreted in light of the model and context under inquiry especially when studying the role of Rb in neuronal survival. There is indeed evidence of age-specific, cell type-specific and region-specific effects following Rb KO in the embryonic and the adult mouse brain. In terms of modeling neurodegenerative processes in human diseases, we discuss cell cycle re-entry (CCE) as a candidate mechanism underlying the increased vulnerability of Rb-deficient neurons to cell death. Notably, mouse models may limit the extent to which CCE due to Rb inactivation can mimic the pathological course of these disorders, such as Alzheimer's disease. These remarks ought to be considered in future research when studying the consequences of Rb inactivation on neuronal generation and survival in rodents and their corresponding clinical significance in humans.http://www.sciencedirect.com/science/article/pii/S2665945X23000025The Retinoblastoma Protein pRbKnock-outMouse modelsNeuronal survivalCell cycle Re-EntryNeurodegeneration |
| spellingShingle | Saad Omais Yara E. El Atie Noël Ghanem Rb deficiency, neuronal survival and neurodegeneration: In search of the perfect mouse model Current Research in Neurobiology The Retinoblastoma Protein pRb Knock-out Mouse models Neuronal survival Cell cycle Re-Entry Neurodegeneration |
| title | Rb deficiency, neuronal survival and neurodegeneration: In search of the perfect mouse model |
| title_full | Rb deficiency, neuronal survival and neurodegeneration: In search of the perfect mouse model |
| title_fullStr | Rb deficiency, neuronal survival and neurodegeneration: In search of the perfect mouse model |
| title_full_unstemmed | Rb deficiency, neuronal survival and neurodegeneration: In search of the perfect mouse model |
| title_short | Rb deficiency, neuronal survival and neurodegeneration: In search of the perfect mouse model |
| title_sort | rb deficiency neuronal survival and neurodegeneration in search of the perfect mouse model |
| topic | The Retinoblastoma Protein pRb Knock-out Mouse models Neuronal survival Cell cycle Re-Entry Neurodegeneration |
| url | http://www.sciencedirect.com/science/article/pii/S2665945X23000025 |
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