PMID- 8674108
OWN - NLM
STAT- MEDLINE
DCOM- 19960814
LR  - 20240104
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 85
IP  - 7
DP  - 1996 Jun 28
TI  - The tumor suppressor gene Brca1 is required for embryonic cellular proliferation 
      in the mouse.
PG  - 1009-23
AB  - Mutations of the BRCA1 gone in humans are associated with predisposition to 
      breast and ovarian cancers. We show here that Brca1+/- mice are normal and 
      fertile and lack tumors by age eleven months. Homozygous Brca1(5-6) mutant mice 
      die before day 7.5 of embryogenesis. Mutant embryos are poorly developed, with no 
      evidence of mesoderm formation. The extraembryonic region is abnormal, but 
      aggregation with wild-type tetraploid embryos does not rescue the lethality. In 
      vivo, mutant embryos do not exhibit increased apoptosis but show reduced cell 
      proliferation accompanied by decreased expression of cyclin E and mdm-2, a 
      regulator of p53 activity. The expression of cyclin-dependent kinase inhibitor 
      p21 is dramatically increased in the mutant embryos. Buttressing these in vivo 
      observations is the fact that mutant blastocyst growth is grossly impaired in 
      vitro. Thus, the death of Brca1(5-6) mutant embryos prior to gastrulation may be 
      due to a failure of the proliferative burst required for the development of the 
      different germ layers.
FAU - Hakem, R
AU  - Hakem R
AD  - Amgen Institute, Toronto, Ontario, Canada.
FAU - de la Pompa, J L
AU  - de la Pompa JL
FAU - Sirard, C
AU  - Sirard C
FAU - Mo, R
AU  - Mo R
FAU - Woo, M
AU  - Woo M
FAU - Hakem, A
AU  - Hakem A
FAU - Wakeham, A
AU  - Wakeham A
FAU - Potter, J
AU  - Potter J
FAU - Reitmair, A
AU  - Reitmair A
FAU - Billia, F
AU  - Billia F
FAU - Firpo, E
AU  - Firpo E
FAU - Hui, C C
AU  - Hui CC
FAU - Roberts, J
AU  - Roberts J
FAU - Rossant, J
AU  - Rossant J
FAU - Mak, T W
AU  - Mak TW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (BRCA1 Protein)
RN  - 0 (Cdkn1a protein, mouse)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Cyclins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.3.2.27 (Mdm2 protein, mouse)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
SB  - IM
MH  - Alternative Splicing/physiology
MH  - Animals
MH  - Apoptosis/genetics
MH  - BRCA1 Protein
MH  - Base Sequence
MH  - Cell Division/genetics
MH  - Cyclin-Dependent Kinase Inhibitor p21
MH  - Cyclins/genetics
MH  - Embryo, Mammalian/*cytology/physiology
MH  - Enzyme Inhibitors/metabolism
MH  - Exons/genetics
MH  - Female
MH  - Gene Expression/physiology
MH  - Genes, Lethal/physiology
MH  - Genes, Tumor Suppressor/genetics
MH  - Genetic Carrier Screening
MH  - Male
MH  - Mammary Neoplasms, Experimental/*genetics
MH  - Mesoderm/cytology/physiology
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Molecular Sequence Data
MH  - Mutation/physiology
MH  - Neoplasm Proteins/*genetics
MH  - *Nuclear Proteins
MH  - Phenotype
MH  - Proto-Oncogene Proteins/genetics
MH  - Proto-Oncogene Proteins c-mdm2
MH  - Transcription Factors/*genetics
MH  - Trophoblasts/cytology/physiology
MH  - Tumor Suppressor Protein p53/genetics
EDAT- 1996/06/28 00:00
MHDA- 1996/06/28 00:01
CRDT- 1996/06/28 00:00
PHST- 1996/06/28 00:00 [pubmed]
PHST- 1996/06/28 00:01 [medline]
PHST- 1996/06/28 00:00 [entrez]
AID - S0092-8674(00)81302-1 [pii]
AID - 10.1016/s0092-8674(00)81302-1 [doi]
PST - ppublish
SO  - Cell. 1996 Jun 28;85(7):1009-23. doi: 10.1016/s0092-8674(00)81302-1.