DOI: 10.1073/pnas.0508500103. Synergistic roles of Mdm2 and Mdm4 for p53 inhibition in central nervous system development

Synergistic roles of Mdm2 and Mdm4 for p53 inhibition in central nervous system development

10.1073/pnas.0508500103

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Loss of Mdm2 or Mdm4 leads to embryo lethal phenotypes that are p53-dependent. To determine whether Mdm2 and Mdm4 inhibit p53 function redundantly in a more restricted cell type, conditional alleles were crossed to a neuronal specific Cre transgene to delete Mdm2 and Mdm4 in the CNS. Mice lacking Mdm2 in the CNS developed hydranencephaly at embryonic day 12.5 due to apoptosis, whereas Mdm4 deletion showed a proencephaly phenotype at embryonic day 17.5 because of cell cycle arrest and apoptosis. The deletion of both genes, strikingly, contributed to an even earlier and more severe CNS phenotype. Additionally, Mdm2 and Mdm4 had a gene dosage effect, because loss of three of the four Mdm alleles also showed a more accelerated CNS phenotype than deletion of either gene alone. All phenotypes were rescued by deletion of p53 . Thus, these in vivo data demonstrate the importance of Mdm4 independent of Mdm2 in inhibition of p53.

Bibliography

Xiong, S., Van Pelt, C. S., Elizondo-Fraire, A. C., Liu, G., & Lozano, G. (2006). Synergistic roles of Mdm2 and Mdm4 for p53 inhibition in central nervous system development. Proceedings of the National Academy of Sciences, 103(9), 3226â3231.

Authors 5

Shunbin Xiong (first)
Carolyn S. Van Pelt (additional)
Ana C. Elizondo-Fraire (additional)
Geng Liu (additional)
Guillermina Lozano (additional)

References 43 Referenced 117

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Dates

Type	When
Created	19 years, 6 months ago (Feb. 21, 2006, 11:03 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 2:08 p.m.)
Indexed	1 month ago (July 23, 2025, 7:59 a.m.)
Issued	19 years, 6 months ago (Feb. 21, 2006)
Published	19 years, 6 months ago (Feb. 21, 2006)
Published Online	19 years, 6 months ago (Feb. 21, 2006)
Published Print	19 years, 6 months ago (Feb. 28, 2006)

Funders 0

None

BibTeX

@article{Xiong_2006, title={Synergistic roles of Mdm2 and Mdm4 for p53 inhibition in central nervous system development}, volume={103}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0508500103}, DOI={10.1073/pnas.0508500103}, number={9}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Xiong, Shunbin and Van Pelt, Carolyn S. and Elizondo-Fraire, Ana C. and Liu, Geng and Lozano, Guillermina}, year={2006}, month=feb, pages={3226–3231} }

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