STOCK Brca1^tm1Aash/J

Stock number: 017835
Product name: Brca1^F22-24
Research areas: Cancer Research, Endocrine Deficiency Research, Research Tools

Description

The Brca1^F22-24 allele has loxP sites flanking exons 22-24 of the Brca1 gene. These mice may be useful in generating tissue-specific BRCA1 deletions for studying basal-like cancer and breast cancer.

Detailed description

The Brca1^{F22-24/F22-24} allele has loxP sites flanking exons 22-24 of the breast cancer 1 gene (Brca1). Homozygous Brca1^{F22-24/F22-24} mice are viable and fertile with no observed abnormalities. When bred to mice that express Cre recombinase, the resulting offspring will have the sequences encoding the second terminal BRCT domain deleted in the cre-expressing tissue(s). These Brca1^{F22-24/F22-24} mice may be useful in generating tissue-specific BRCA1 deletions for studying human basal-like cancer and breast cancer.

For example, when crossed to a strain expressing Cre recombinase in mammary gland during lactation (see Stock No. 017836), mice exhibit increased mammary gland tumor incidence.

Development

The Brca1^F22-24 targeted mutation was designed by Dr. Alan Ashworth (Breakthrough Breast Cancer Research Centre, London) to replace exons 22-24 of the mouse breast cancer 1 gene (Brca1) with a loxP site, a cDNA sequence encoded by exons 22-24, a 3' myc epitope, bovine growth hormone polyA signal, a second loxP site, a splice acceptor sequence, and a PGK-neo cassette. This construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting chimeric mice were bred to C57BL/6 mice. These mice were intercrossed to establish a colony of Brca1^{F22-24/F22-24} mice on a mixed background.

Brca1^F22-24 mice were bred to C57BL/6;129S7-Trp53^tm1Brd and C57BL/6;CBA-Tg(LGB-cre)74Acl mice, and the resulting triple mutant mice were sent to The Jackson Laboratory Repository as Stock No. 012620. Upon arrival, some mice were selectively bred with wildtype mice from the colony or with C57BL/6J inbred mice (Stock No. 000664) to generate this Brca1^F22-24 single mutant colony (as Stock No. 017835).

Allele

Symbol: Brca1^tm1Aash
Name: targeted mutation 1, Alan Ashworth
MGI accession ID: MGI:3706167
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: Brca1^F22-24
Marker symbol: Brca1
Marker name: breast cancer 1, early onset
Marker synonyms: BRCA-1; BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4; PPP1R53; PSCP; RNF53
Chromosome: 11
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Site of expression: mammary epithelial cells
Molecular note: Exons 22-24 were replaced with a floxed sequence containing cDNA for exons 22-24 with an in frame myc epitope and a bovine growth hormone poly A sequence. This vector allows conditional excision of the second, terminal BRCT domain. Downstream of the floxed sequence, a splice acceptor and PGK-neo were inserted.