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The Brca1S1598F allele was generated to replace the natural serine codon for Brca1 amino acid residue 1598 with a phenylalanine codon. Thus, Brca1S1598A encodes a full-length Brca1 polypeptide (1812 amino acids) which is predicted to contain S1598F, a missense mutation modeled after the pathogenic BRCA1-S1655F mutation implicated in human hereditary breast and ovarian cancer. Structural and biochemical studies have established that this mutation abrogates the interaction of BRCA1 protein with its BRCT phospho-ligands, including Abraxas, BRIP1, and CtIP. Of note, the Brca1S1598F allele retains the original loxP-neomycin-loxP (LNL) gene cassette in intron 16, which does not affect the expression of the Brca1-S1598F protein.
The S1598F mutation was introduced into exon 16 by site-directed mutagenesis. For the target construct, a neomycin cassette, flanked by loxP sites was inserted into intron 16, and a diphtheria toxin gene cassette (DT) was included as a negative selection marker. The targeting construct was electroporated into KV1 ES cells derived from (C57BL/6J x 129S6/SvEvTac)F1. Two independent neomycin-resistant ES clones were genotyped for the Brca1SF-neo knock-in allele and injected into C57BL/6J blastocysts. Germline-transformed Brca1SF-neo/+ heterozygous mice backcrossed with C57BL/6J to N4.
Shakya R, Reid LJ, Reczek CR, Cole F, Egli D, Lin CS, deRooij DG, Hirsch S, Ravi K, Hicks JB, Szabolcs M, Jasin M, Baer R, Ludwig T. BRCA1 tumor suppression depends on BRCT phosphoprotein binding, but not its E3 ligase activity. Science. 2011 Oct 28;334(6055):525-8. doi: 10.1126/science.1209909. (Medline PMID: 22034435)
Billing D, Horiguchi M, Wu-Baer F, Taglialatela A, Leuzzi G, Nanez SA, Jiang W, Zha S, Szabolcs M, Lin CS, Ciccia A, Baer R. The BRCT Domains of the BRCA1 and BARD1 Tumor Suppressors Differentially Regulate Homology-Directed Repair and Stalled Fork Protection. Mol Cell. 2018 Oct 4;72(1):127-139.e8. doi: 10.1016/j.molcel.2018.08.016. Epub 2018 Sep 20. (Medline PMID: 30244837)
Colony Surveillance Program and Current Health Reports
Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.
Cryopreserved material may be available upon request, please inquire to mmrrc@missouri.edu for more information.
A Commercial License Agreement from the Donor is required for for-profit entities to use this strain. For more information, please contact Joan Jose Martinez.
Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.
A Commercial License Agreement from the Donor is required for for-profit entities to use this strain. For more information, please contact Joan Jose Martinez
Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.
1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.
2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.
3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.
4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.