These mice carry the beta-lactoglobulin Cre (BLG-Cre) transgene, are homozygous for floxed exons 22-24 of the breast cancer 1 (Brca1) allele, and are heterozygous for p53 tumor-suppressor gene (Trp53) deficiency. This strain may be useful for studying human basal-like cancer and breast cancer, as well as providing a useful tool for testing new therapeutics.
Afshan McCarthy, The Breakthrough Toby Robins Breast Canc
Genetic Background | Generation |
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F?+F26
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Trp53 | transformation related protein 53 |
Allele Type |
---|
Transgenic (Recombinase-expressing) |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Conditional ready (e.g. floxed), No functional change) | Brca1 | breast cancer 1, early onset |
Starting at:
$278.00 Domestic price for female 4-week |
556.00 Domestic price for breeder pair |
To induce the tumor development in these mice, the donating investigator reports that BLG-Cre; Brca1tm1Aash; Trp53+/- mice should be allowed to go through two rounds of pregnancy and then set aside to allow Cre activation and the loss of Brca1 function.
BLG-Cre; Brca1tm1Aash; Trp53+/- mice that carry the beta-lactoglobulin Cre (BLG-Cre) transgene are homozygous for floxed exons 22-24 of the breast cancer 1 (Brca1) allele, and are heterozygous for p53 tumor-suppressor gene (Trp53) deficiency. Mice of this genotype are viable, fertile, normal in size and do not display any behavioral abnormalities. BLG-Cre; Brca1tm1Aash; Trp53+/- females have expression of the BLG-Cre transgene during lactation; which leads to loss of Brca1 function in the mammary gland. This results in formation of mammary tumors exhibiting high grade central necrosis and metaplastic elements in the form of spindle cell and squamous cell differentiation; as seen in human basal-like breast cancers and BRCA1 mutation carriers. Heterozygosity for the mutant p53 allele accelerates the formation of mammary tumors. This strain may be useful for studying human basal-like cancer and breast cancer, as well as providing a useful tool for testing new therapeutics.
This mouse colony harbors three mutations: a p53- mutation, the Brca1F22-24 mutation, and a BLG-Cre transgene. The description of each is below.
To generate the p53 mutant allele, a targeting vector was designed to replace part of exon 5 of the mouse p53 tumor-suppressor gene, p53, with a PolII-neomycin (neo) resistance cassette (Harvey et al, Nat Gen, 1993; 5; 225-29). This construct was electroporated into 129S7/SvEvBrd-Hprt1+-derived AB1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to C57BL/6 females. These mice were intercrossed to establish a colony of p53 transgenic mice.
To generate the Brca1F22-24 mutant allele, a targeting vector 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 Brca1F22-24/F22-24 mice on a mixed background.
The BLG-Cre transgene was designed by Dr. Alan R. Clarke (while at University Medical School, Edinburgh, United Kingdom) to have Cre recombinase under the control of the sheep mammary gland specific promoter of the ovine beta-lactoglobulin (BLG) gene. The construct included exon 1 of sheep BLG, and a Cre recombinase with a modified initiation codon and a polyadenylation signal (polyA). The construct was microinjected into the pronuclei of (CBA x C57BL/6) fertilized oocytes, and mice from founder line 74 were identified and bred to C57BL/6 mice. These mice were intercrossed to establish a colony of BLG-cre mice on a mixed background.
Mutant mice were bred together to generate the triple mutant colony. Mice heterozygous for the p53 allele, homozygous for the floxed Brca1 allele (Brca1F22-24/F22-24), and hemizygous for the BLG-cre transgene (also called BLG-Cre; Brca1F22-24/F22-24; p53+/- mice) were maintained on a mixed genetic background prior to sending to The Jackson Laboratory Repository. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
Expressed Gene | cre, cre recombinase, bacteriophage P1 |
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Site of Expression | Cre recombinase is active in the mammary gland. |
Site of Expression | mammary epithelial cells |
Allele Name | targeted mutation 1, Allan Bradley |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | P-; p53-; p53N; Trp53-; Trp53delta; Trp53N; TSG-p53 |
Gene Symbol and Name | Trp53, transformation related protein 53 |
Gene Synonym(s) | |
Site of Expression | Normal Trp53 expression is widespread. |
Strain of Origin | 129S7/SvEvBrd-Hprt+ |
Chromosome | 11 |
Molecular Note | A PolII-neomycin resistance cassette which lacked a polyadenylation signal was inserted into exon 5 of the gene. The insertion was accompanied by a small deletion of a 450 bp fragment containing 106 nucleotides of exon 5 and 350 nucleotides of intron 4. |
Allele Name | transgene insertion 74, Alan R Clarke |
---|---|
Allele Type | Transgenic (Recombinase-expressing) |
Allele Synonym(s) | BLG-Cre; Blg-CreTg |
Gene Symbol and Name | Tg(LGB-cre)74Acl, transgene insertion 74, Alan R Clarke |
Gene Synonym(s) | |
Promoter | LGB, beta-lactoglobulin, sheep |
Expressed Gene | cre, cre recombinase, bacteriophage P1 |
Site of Expression | Cre recombinase is active in the mammary gland. |
Strain of Origin | (CBA x C57BL/6) |
Chromosome | UN |
Molecular Note | This transgene expresses Cre recombinase under the control of a sheep beta-lactoglobulin promoter (LGB), active in the mammary gland. |
Mutations Made By | Alan Clarke, University Medical School, Edinburgh, Un |
Allele Name | targeted mutation 1, Alan Ashworth |
---|---|
Allele Type | Targeted (Conditional ready (e.g. floxed), No functional change) |
Allele Synonym(s) | Brca1F22-24 |
Gene Symbol and Name | Brca1, breast cancer 1, early onset |
Gene Synonym(s) | |
Site of Expression | mammary epithelial cells |
Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl+ |
Chromosome | 11 |
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. |
Mutations Made By | Alan Ashworth, University of California, San Francisco |
To induce the tumor development in these mice, the donating investigator reports that BLG-Cre; Brca1F22-24/F22-24; p53+/- mice should be allowed to go through two rounds of pregnancy and then set aside to allow Cre activation and the loss of Brca1 function.
When using the BLG-Cre; Brca1F22-24; p53 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #012620 in your Materials and Methods section.
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Trp53<tm1Brd>, Heterozygous or wildtype for Brca1<tm1Aash>, Hemizygous or Non carrier for Tg(LGB-cre)74Acl/ |
Frozen Mouse Embryo | STOCK Trp53<tm1Brd> Brca1<tm1Aash> Tg(LGB-cre)74Acl/J Frozen | $2595.00 |
Frozen Mouse Embryo | STOCK Trp53<tm1Brd> Brca1<tm1Aash> Tg(LGB-cre)74Acl/J Frozen | $2595.00 |
Frozen Mouse Embryo | STOCK Trp53<tm1Brd> Brca1<tm1Aash> Tg(LGB-cre)74Acl/J Frozen | $3373.50 |
Frozen Mouse Embryo | STOCK Trp53<tm1Brd> Brca1<tm1Aash> Tg(LGB-cre)74Acl/J Frozen | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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