BRCA2 deficiency in mice leads to meiotic impairment and infertility

Shyam K. Sharan, April Pyle, Vincenzo Coppola, Janice Babus, Srividya Swaminathan, Jamie Benedict, Deborah Swing, Betty K. Martin, Lino Tessarollo, Janice P. Evans, Jodi A. Flaws, Mary Ann Handel

Research output: Contribution to journalReview article

Abstract

The role of Brca2 in gametogenesis has been obscure because of embryonic lethality of the knockout mice. We generated Brca2-null mice carrying a human BAC with the BRCA2 gene. This construct rescues embryonic lethality and the mice develop normally. However, there is poor expression of the transgene in the gonads and the mice are infertile, allowing examination of the function of BRCA2 in gametogenesis. BRCA2-deficient spermatocytes fail to progress beyond the early prophase I stage of meiosis. Observations on localization of recombination-related and spermatogenic-related proteins suggest that the spermatocytes undergo early steps of recombination (DNA double strand break formation), but fail to complete recombination or initiate spermiogenic development. In contrast to the early meiotic prophase arrest of spermatocytes, some mutant oocytes can progress through meiotic prophase I, albeit with a high frequency of nuclear abnormalities, and can be fertilized and produce embryos. Nonetheless, there is marked depletion of germ cells in adult females. These studies provide evidence for key roles of the BRCA2 protein in mammalian gametogenesis and meiotic success.

Original languageEnglish (US)
Pages (from-to)131-142
Number of pages12
JournalDevelopment
Volume131
Issue number1
DOIs
StatePublished - Jan 2004

Keywords

  • BRCA2
  • DNA repair
  • Meiosis
  • Oogenesis
  • Spermatogenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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