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Human BRCA1 gene rescues the embryonic lethality of Brca1 mutant mice

  1. Author:
    Chandler, J.
    Hohenstein, P.
    Swing, D. A.
    Tessarollo, L.
    Sharan, S. K.

  2. Author Address

    NCI, Mouse Canc Genet Program, Frederick Canc Res & Dev Ctr, POB B, Frederick, MD 21702 USA. NCI, Mouse Canc Genet Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Leiden Univ, Med Ctr, Dept Pathol, Pathophysiol Growth & Differentiat, Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Human & Clin Genet, Ctr Med Genet, Leiden, Netherlands. Sharan SK NCI, Mouse Canc Genet Program, Frederick Canc Res & Dev Ctr, POB B, Frederick, MD 21702 USA.
    1. Year: 2001
  2. Journal: Genesis
    1. 29
    2. 2
    3. Pages: 72-77
  4. Type of Article: Article
  1. Abstract:

    Half of all familial breast cancers are due to mutation in the BRCA1 gene. However, despite its importance, attempts to model BRCA1-induced disease in the mouse have been disappointing. Heterozygous Brca1 knockout mice do not develop mammary tumors and homozygous knockout mice die during embryogenesis from ill- defined causes. Sequence analysis has shown that the coding region, genomic organization, and regulatory sequences of the human and mouse genes are not well conserved. This has raised the question of whether the mouse can serve as an effective model for functional analysis of the human BRCA1 gene. To address this question we have introduced a bacterial artificial chromosome containing the human BRCA1 gene into the germline of Brca1 knockout mice. Surprisingly, we have found that the embryonic lethality of Brca1 knockout mice is rescued by the human transgene. We also show that expression of human BRCA1 transgene mirrors the endogenous murine gene. Our "humanized" transgenic mice can serve as a model system for functional analyses of the human BRCA1 gene. genesis 29:72-77, 2001. Published 2001 Wiley-Liss, Inc.(dagger).

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