GFP reporter mice for the retinoblastoma-related cell cycle regulator p107.
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.
Burkhart
Deborah L
DL
Department of Pediatrics and Genetics, Cancer Biology Program, Stanford Medical School, Stanford, California, USA.
Viatour
Patrick
P
Ho
Victoria M
VM
Sage
Julien
J
D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics*; D022781:Hepatocytes / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D016160:Retinoblastoma Protein / Q000235:genetics; D050720:Retinoblastoma-Like Protein p107 / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes; D015854:Up-Regulation
D016160:Retinoblastoma Protein; D050720:Retinoblastoma-Like Protein p107; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins