Brca1 deficiency results in early embryonic lethality characterized by neuroepithelial abnormalities

Nat Genet. 1996 Feb;12(2):191-4. doi: 10.1038/ng0296-191.


The breast and ovarian cancer susceptibility gene, BRCA1, has been cloned and shown to encode a zinc-finger protein of unknown function. Mutations in BRCA1 account for at least 80% of families with both breast and ovarian cancer, as well as some non-familial sporadic ovarian cancers. The loss of wild-type BRCA1 in tumours of individuals carrying one nonfunctional BRCA1 allele suggests that BRCA1 encodes a tumour suppressor that may inhibit the proliferation of mammary epithelial cells. 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 Brca1 allele. Analysis of mice homozygous for the mutant allele indicate that Brca1 is critical for normal development, as these mice died in utero between 10 and 13 days of gestation (E10-E13). Abnormalities in Brca1-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 Brca1-deficient embryos appeared disorganized, with signs of both rapid proliferation and excessive cell death.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anencephaly / embryology
  • Anencephaly / genetics
  • Animals
  • BRCA1 Protein
  • Base Sequence
  • Central Nervous System / embryology*
  • Embryonic and Fetal Development / genetics*
  • Epithelium / embryology
  • Female
  • Gene Targeting
  • Genes, Lethal
  • Homozygote
  • Male
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • RNA, Messenger / analysis
  • Spinal Dysraphism / embryology
  • Spinal Dysraphism / genetics
  • Transcription Factors / genetics
  • Transcription Factors / physiology*


  • BRCA1 Protein
  • Neoplasm Proteins
  • RNA, Messenger
  • Transcription Factors