Brca1 deficiency results in early embryonic lethality characterized by neuroepithelial abnormalities (original) (raw)

Nature Genetics volume 12, pages 191–194 (1996)Cite this article

Abstract

The breast and ovarian cancer susceptibility gene, BRCA1, has been cloned and shown to encode a zinc-finger protein of unknown function1. Mutations in BRCA1 account for at least 80% of families with both breast and ovarian cancer, as well as some non-familial sporadic ovarian cancers2,3. The loss of wild-type BRCA1 in tumours of individuals carrying one nonfunctional BRCA1 allele suggests that BRCA1 encodes a tumour suppressor4–6 that may inhibit the proliferation of mammary epithelial cells7. To examine the role of BRCA1 in normal tissue growth and differentiation, and to generate a potential model for the cancer susceptibility associated with loss of BRCA1 function, we have created a mouse line carrying a mutation in one Brcal allele. Analysis of mice homozygous for the mutant allele indicate that Brcal is critical for normal development, as these mice died in utero between 10 and 13 days of gestation (E10–E13). Abnormalities in Brcal -deficient embryos were most evident in the neural tube, with 40% of the embryos presenting with varying degrees of spina bifida and anencephaly. In addition, the neuroepithelium in Brca 1-deficient embryos appeared disorganized, with signs of both rapid proliferation and excessive cell death.

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Authors and Affiliations

  1. Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina, USA
    Lori C. Gowen & Beverly H. Koller
  2. Department of Medicine University of North Carolina, Chapel Hill, North Carolina, USA
    B. Lee Johnson, Anne M. Latour & Beverly H. Koller
  3. Department of Cell Biology and Anatomy University of North Carolina, Chapel Hill, North Carolina, USA
    Kathleen K. Sulik

Authors

  1. Lori C. Gowen
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  2. B. Lee Johnson
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  3. Anne M. Latour
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  4. Kathleen K. Sulik
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  5. Beverly H. Koller
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Gowen, L., Johnson, B., Latour, A. et al. Brca1 deficiency results in early embryonic lethality characterized by neuroepithelial abnormalities.Nat Genet 12, 191–194 (1996). https://doi.org/10.1038/ng0296-191

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