| First Author | Migliorini D | Year | 2002 |
| Journal | Mol Cell Biol | Volume | 22 |
| Issue | 15 | Pages | 5527-38 |
| PubMed ID | 12101245 | Mgi Jnum | J:77907 |
| Mgi Id | MGI:2182884 | Doi | 10.1128/MCB.22.15.5527-5538.2002 |
| Citation | Migliorini D, et al. (2002) Mdm4 (Mdmx) regulates p53-induced growth arrest and neuronal cell death during early embryonic mouse development. Mol Cell Biol 22(15):5527-38 |
| abstractText | We report here the characterization of a mutant mouse line with a specific gene trap event in the Mdm4 locus. Absence of Mdm4 expression results in embryonic lethality (10.5 days postcoitum [dpc]), which was rescued by transferring the Mdm4 mutation into a Trp53-null background. Mutant embryos were characterized by overall growth deficiency, anemia, improper neural tube closure, and dilation of lateral ventricles. In situ analysis demonstrated increased levels of p21(CIP1/Waf1) and lower levels of Cyclin E and proliferating cell nuclear antigen expression. Consistent with lack of 5-bromo-2'-deoxyuridine incorporation, these data suggest a block of mutant embryo cells in the G(1) phase of the cell cycle. Accordingly, Mdm4-deficient mouse embryonic fibroblasts manifested a greatly reduced proliferative capacity in culture. Moreover, extensive p53-dependent cell death was specifically detected in the developing central nervous system of the Mdm4 mutant embryos. These findings unambiguously assign a critical role for Mdm4 as a negative regulator of p53 and suggest that Mdm4 could contribute to neoplasias retaining wild-type Trp53. Finally, we provide evidence indicating that Mdm4 plays no role on cell proliferation or cell cycle control that is distinct from its ability to modulate p53 function. |
