MDM2 EXPRESSION DURING MOUSE EMBRYOGENESIS AND THE REQUIREMENT OF P53

We compared mouse embryonic expression of the MDM2 proto-oncogene, p21 (WAF1/CIP1) and their transcriptional regulator, p53. MDM2 expression is ubiquitous from 7.5 to 11.5 days post coitum (dpc) and more restric ted from 12.5 dpc, with the highest levels in the testes and neural tu be. From 14.5 to 18.5 dpc, the nasal respiratory epithelium expresses high levels of MDM2 RNA and protein and p21(WAF1/CIP1) RNA, in both wi ld type and p53 null embryos. MDM2 expression during development is ti ssue-specific and, like p21(WAF1/CIP1), is independent of p53. MDM2 ma y have a developmental role after 6.5 dpc, when MDM2 null mice die (Jo nes, S.N., Roe, A.E., Donehower, L.A., Bradley, A., 1995. Rescue of em bryonic lethality in Mdm2-deficient mice by absence of p53. Nature 378 , 206-208; Montes de Oca Luna, R., Wagner, D.S., Lozano, G., 1995. Res cue of early embryonic lethality in mdm2-deficient mice by deletion of p53. Nature 378, 203-206). (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.