Brca2 is required for embryonic cellular proliferation in the mouse

Akira Suzuki, José Luis De La Pompa, Razqallah Hakem, Andrew Elia, Ritsuko Yoshida, Kong Mo, Hiroshi Nishina, Tony Chuang, Andrew Wakeham, Annick Itie, Wilson Koo, Phyllis Billia, Alexandra Ho, Manabu Fukumoto, Chi Chung Hui, Tak W. Mak

Research output: Contribution to journalArticlepeer-review

220 Citations (Scopus)

Abstract

Mutations of the tumor suppressor gene BRCA2 are associated with predisposition to breast and other cancers. Homozygous mutant mice in which exons 10 and 11 of the Brca2 gene were deleted by gene targeting (Brca210- 11) die before day 9.5 of embryogenesis. Mutant phenotypes range from severely developmentally retarded embryos that do not gastrulate to embryos with reduced size that make mesoderm and survive until 8.5 days of development. Although apoptosis is normal, cellular proliferation is impaired in Brca210-11 mutants, both in vivo and in vitro. In addition, the expression of the cyclin-dependent kinase inhibitor p21 is increased. Thus, Brca210-11 mutants are similar in phenotype to Brca15-6 mutants but less severely affected. Expression of either of these two genes was unaffected in mutant embryos of the other. This study shows that Brca2, like Brca1, is required for cellular proliferation during embryogenesis. The similarity in phenotype between Brca1 and Brca2 mutants suggests that these genes may have cooperative roles or convergent functions during embryogenesis.

Original languageEnglish
Pages (from-to)1242-1252
Number of pages11
JournalGenes and Development
Volume11
Issue number10
DOIs
Publication statusPublished - 1997 May 15

Keywords

  • Brca2 mutant mice
  • embryogenesis
  • p21
  • proliferation

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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