5933

RBL1

CP107|PRB1|p107;retinoblastoma-like 1 (p107);RBL1;retinoblastoma-like 1 (p107)

107 kDa retinoblastoma-associated protein|cellular protein 107|retinoblastoma-like protein 1

20q11.2

protein-coding

One major factor hindering progress of pediatric cancers of the nervous system has been the lack of satisfactory model systems for testing novel therapies. A mouse strain, mutant for the Rb1 gene was generated 12 years ago in the hope of producing a model in which to study retinoblastoma. Surprisingly, the Rb(+/-) mice never developed retinoblastoma. Now, Zhang, Schweers and Dyer produce triply deficient Rb, p107 and p53 mutant retinal progenitor cells. ALL such mice develop intraocular retinoblastoma with invasion of the tumor into the anterior chamber of the eye. This dramatic finding represents the first description of a heritable mouse model of retinoblastoma, which has eluded investigators for the last 12 years. Such models provide an unprecedented opportunity to advance knowledge of tumorigenesis and to develop non-toxic intervention strategies which eradicate disease.

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 isincreased 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.