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BRCA2 deficiency in mice leads to meiotic impairment and infertility

  1. Author:
    Sharan, S. K.
    Pyle, A.
    Coppola, V.
    Babus, J.
    Swaminathan, S.
    Benedict, J.
    Swing, D.
    Martin, B. K.
    Tessarollo, L.
    Evans, J. P.
    Flaws, J. A.
    H, el

  2. Author Address

    Sharan, SK, NCI, Mouse Canc Genet Program, Ctr Canc Res, 1050 Boyles St, Frederick, MD 21702 USA NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. Univ Tennessee, Dept Biochem & Cellular & Mol Biol, Knoxville, TN 37996 USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. Johns Hopkins Univ, Bllomberg Sch Publ Hlth, Dept Biochem & Mol Biol, Div Reprod Biol, Baltimore, MD 21205 USA.
    1. Year: 2004
  2. Journal: Development
    1. 131
    2. 1
    3. Pages: 131-142
  4. Type of Article: Article
  1. 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

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