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Updated: Jul 2, 2026
Transpupillary Two-Photon In Vivo Imaging of the Mouse Retina
Published on: February 13, 2021
GFP reporter mice for the retinoblastoma-related cell cycle regulator p107
Deborah L Burkhart1, Patrick Viatour, Victoria M Ho
1Department of Pediatrics and Genetics, Cancer Biology Program, Stanford Medical School, Stanford, California, USA.
Abstract:
The RB tumor suppressor gene is mutated in a broad range of human cancers, including pediatric retinoblastoma. Strikingly, however, Rb mutant mice develop tumors of the pituitary and thyroid glands, but not retinoblastoma. Mouse genetics experiments have demonstrated that p107, a protein related to pRB, is capable of preventing retinoblastoma, but not pituitary tumors, in Rb-deficient mice. Evidence suggests that the basis for this compensatory function of p107 is increased transcription of the p107 gene in response to Rb inactivation. To begin to address the context-dependency of this compensatory role of p107 and to follow p107 expression in vivo, we have generated transgenic mice carrying an enhanced GFP (eGFP) reporter inserted into a bacterial artificial chromosome (BAC) containing the mouse p107 gene. Expression of the eGFP transgene parallels that of p107 in these transgenic mice and identifies cells with a broad range of expression level for p107, even within particular organs or tissues. We also show that loss of Rb results in the upregulation of p107 transcription in specific cell populations in vivo, including subpopulations of hematopoietic cells. Thus, p107 BAC-eGFP transgenic mice serve as a useful tool to identify distinct cell types in which p107 is expressed and may have key functions in vivo, and to characterize changes in cellular networks accompanying Rb deficiency.
Insights
The RB tumor suppressor gene is crucial for preventing retinoblastoma. In Rb-deficient mice, the related p107 protein compensates, preventing retinoblastoma but not pituitary tumors, with its expression increasing upon Rb loss.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The RB tumor suppressor gene is frequently mutated in human cancers, including retinoblastoma.
- Rb-deficient mice develop pituitary and thyroid tumors, but not retinoblastoma, suggesting compensatory mechanisms.
- The related protein p107 can prevent retinoblastoma in Rb-deficient mice, indicating a compensatory role.
Purpose of the Study:
- To investigate the context-dependency of p107's compensatory role in Rb-deficient mice.
- To track p107 expression in vivo and identify specific cell populations involved in Rb deficiency.
- To develop a tool for studying cellular network changes associated with Rb loss.
Main Methods:
- Generation of transgenic mice carrying a p107 bacterial artificial chromosome (BAC) with an enhanced GFP (eGFP) reporter.
- Monitoring eGFP expression as a proxy for endogenous p107 expression in vivo.
- Analyzing p107 gene transcription upregulation in response to Rb loss in specific cell types.
Main Results:
- eGFP expression in p107 BAC-eGFP mice accurately reflects endogenous p107 expression patterns across various tissues.
- Loss of Rb leads to increased p107 transcription in specific cell populations, including hematopoietic cells.
- The p107 BAC-eGFP mice successfully identify distinct cell types with p107 expression and potential roles in Rb deficiency.
Conclusions:
- p107 plays a compensatory role in preventing retinoblastoma in Rb-deficient contexts.
- Rb deficiency triggers p107 upregulation in specific cellular compartments, highlighting context-dependent regulation.
- p107 BAC-eGFP transgenic mice are valuable tools for dissecting p107 function and cellular network dynamics in Rb-deficient states.
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