Partial rescue of Brca15–6 early embryonic lethality by p53 or p21 null mutation (original) (raw)
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- Published: 01 July 1997
Nature Genetics volume 16, pages 298–302 (1997)Cite this article
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Abstract
Mutations in the mouse Brca1 gene cause lethality at different embryonic stages1–3. We have shown that Brca15–6 mutant embryos, in which the fifth and sixth exons of Brcal are deleted, die before E7.5 and show decreased cellular proliferation2. Brca15–6 mutants also show decreased expression of mdm2, a gene encoding an inhibitor of_p53_ activity4. Thus, we have proposed that the reduction in mdm2 expression in Brca15–6 mutants might lead to increased p53 activity. Consistent with this finding, the expression of p21, which encodes a G1 cell cycle inhibitor5–10 and is a target for p53 transcriptional activation, was dramatically increased in the Brca15–6 mutants, suggesting that impaired cellular proliferation could be due to a G1 cell-cycle arrest, caused by increased p21 levels. To test this hypothesis, we generated mice double mutant for Brca15–6 and p53, or Brca15–6 and p21. Mutation in either p53 or p21 prolonged the survival of Brca15–6 mutant embryos from E7.5 to E9.5. The development of most Brca15–6: p21 double-mutant embryos was comparable to that of their wild-type littermates, although no mutant survived past E10.5. The fact that mutation of neither p53 nor p21 completely rescued Brca15–6 embryos suggests that their lethality is likely due to a multi-factorial process.
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Authors and Affiliations
- Amgen Institute, 620 University Avenue, Toronto, M5G2C1, Ontario, Canada
Razqallah Hakem, José Luis de la Pompa, Andrew Elia, Julia Potter & Tak W. Mak - Ontario Cancer Institute, and Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, M5G 2C1, Ontario, Canada
Razqallah Hakem, José Luis de la Pompa, Andrew Elia, Julia Potter & Tak W. Mak
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- Razqallah Hakem
You can also search for this author inPubMed Google Scholar - José Luis de la Pompa
You can also search for this author inPubMed Google Scholar - Andrew Elia
You can also search for this author inPubMed Google Scholar - Julia Potter
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Hakem, R., de la Pompa, J., Elia, A. et al. Partial rescue of _Brca1_5–6 early embryonic lethality by p53 or p21 null mutation.Nat Genet 16, 298–302 (1997). https://doi.org/10.1038/ng0797-298
- Received: 15 April 1997
- Accepted: 05 June 1997
- Issue Date: 01 July 1997
- DOI: https://doi.org/10.1038/ng0797-298