Isolation of the mouse homologue of BRCA1 and genetic mapping to mouse chromosome 11.
The BRCA1 gene is in large part responsible for hereditary human breast and ovarian cancer. Here we report the isolation of the murine Brca1 homologue cDNA clones. In addition, we identified genomic P1 clones that contain most, if not all, of the mouse Brca1 locus. DNA sequence analysis revealed that the mouse and human coding regions are 75% identical at the nucleotide level while the predicted amino acid identity is only 58%. A DNA sequence variant in the Brca1 locus was identified and used to map this gene on a (Mus m. musculus Czech II x C57BL/KsJ)F1 x C57BL/KsJ intersubspecific backcross to distal mouse chromosome 11. The mapping of this gene to a region highly syntenic with human chromosome 17, coupled with Southern and Northern analyses, confirms that we isolated the murine Brca1 homologue rather than a related RING finger gene. The isolation of the mouse Brca1 homologue will facilitate the creation of mouse models for germline BRCA1 defects.
Bennett
L M
LM
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Haugen-Strano
A
A
Cochran
C
C
Brownlee
H A
HA
Fiedorek
F T
FT
Wiseman
R W
RW
D000595:Amino Acid Sequence; D000818:Animals; D019313:BRCA1 Protein; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D001943:Breast Neoplasms / Q000235:genetics; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D003433:Crosses, Genetic; D017931:DNA Primers; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice / Q000235:genetics*; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics*
D019313:BRCA1 Protein; C000605931:Brca1 protein, mouse; D017931:DNA Primers; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins