First Author | Holmberg C | Year | 1998 |
Journal | Oncogene | Volume | 17 |
Issue | 2 | Pages | 143-55 |
PubMed ID | 9674698 | Mgi Jnum | J:89021 |
Mgi Id | MGI:3037615 | Doi | 10.1038/sj.onc.1201915 |
Citation | Holmberg C, et al. (1998) E2F-1-induced p53-independent apoptosis in transgenic mice. Oncogene 17(2):143-55 |
abstractText | The E2F transcription factors are key targets for the retinoblastoma protein, pRB. By inactivation of E2Fs, pRB prevents progression to the S phase. To test proliferative functions of E2F, we generated transgenic mice expressing human E2F-1 and/or human DP-1. When the hydroxymethyl glutaryl coenzyme A reductase promoter was used to express DP-1, overexpression occurred in a variety of tissues and did not confer phenotypic changes. In contrast, expression of E2F-1 from the same promoter was obtained only in testicles, in which E2F-1 overexpression caused atrophy and sterility through a process involving increased apoptosis in the germinal epithelium. This effect was potentiated by simultaneous overexpression of DP-1. Testicular atrophy as a result of overexpression of E2F-1 and DP-1 is independent of functional p53, since p53-nullizygous transgenic mice overexpressing E2F-1 and DP-1 also suffered testicular atrophy. |