Strain Name:
STOCK Brca1tm4.1Rjbr/Mmjax
Stock Number:
069514-JAX
Citation ID:
RRID:MMRRC_069514-JAX
Other Names:
Brca1FH-WT

Strain Information

Brca1tm4.1Rjbr
Name: breast cancer 1, early onset; targeted mutation 4.1, Richard J Baer
Synonyms: Brca1FH-WT
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 11
Alteration at locus: Knock-In
Brca1
Name: breast cancer 1, early onset
Type: Gene
Species: Mouse
Chromosome: 11
Alteration at locus: Knock-In
NCBI: 12189
HGNC: HGNC:1100
Homologene: 5276
Genetic Alterations

The Brca1FH-WT allele introduces an artificial initiator methionine and the FLAG and HA amino acid epitopes (FH, MDYKDDDDKYPYDVPDYA), immediately upstream of the natural initiator methionine codon in exon 2 of the Brca1 gene, as well as a cassette encoding diphtheria toxin A as a negative selection marker. The homology arms of the pBrca1FH-WT-hyg targeting constructs were derived from subcloned fragments of murine 129/Sv genomic DNA encompassing Brca1 exons 1 and 2. In the final constructs, the homology fragment was interrupted in intron 1 by insertion of an FRT-flanked cassette consisting of an artificial splice acceptor site and a promoterless hygromycin resistance gene.

This allele serves as a wild-type control for the Brca1FH-I26A allele (MMRRC:69515), which encodes an FH-tagged Brca1protein harboring Ile26Ala, a missense mutation in the RING domain of Brca1 that abrogates the ubiquitin E3 ligase activity of Brca1 by disrupting its interaction with ubiquitin E2 conjugases.

Genotype Determination
ES Cell Line
Not specified
Phenotype
Heterozygous (Brca1FH-WT/+) and homozygote (Brca1FH-WT/FH-WT) mice develop normally and are fertile.
MeSH Terms
  • Animals
  • BRCA1 Protein/genetics
  • BRCA1 Protein/metabolism
  • Breast Neoplasms/genetics
  • Breast Neoplasms/metabolism
  • Breast Neoplasms/pathology
  • Cell Line
  • Chromosome Aberrations/chemically induced
  • Chromosome Aberrations/drug effects
  • Chromosome Aberrations/radiation effects
  • Cross-Linking Reagents/pharmacology
  • DNA Breaks, Double-Stranded/drug effects
  • DNA Breaks, Double-Stranded/radiation effects
  • DNA Repair/drug effects
  • DNA Repair/genetics
  • DNA Repair/radiation effects
  • Embryonic Stem Cells/metabolism
  • Embryonic Stem Cells/pathology
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Mammary Neoplasms, Animal/genetics
  • Mammary Neoplasms, Animal/metabolism
  • Mammary Neoplasms, Animal/pathology
  • Mice
  • Mitomycin/pharmacology
  • Ovarian Neoplasms/genetics
  • Ovarian Neoplasms/metabolism
  • Ovarian Neoplasms/pathology
  • Rad51 Recombinase/genetics
  • Rad51 Recombinase/metabolism
  • Radiation, Ionizing
  • Recombination, Genetic/drug effects
  • Recombination, Genetic/genetics
  • Recombination, Genetic/radiation effects
  • Tumor Suppressor Proteins/genetics
  • Tumor Suppressor Proteins/metabolism
  • Ubiquitin-Protein Ligases/genetics
  • Ubiquitin-Protein Ligases/metabolism
  • BRCA1 Protein/chemistry
  • Basic-Leucine Zipper Transcription Factors/genetics
  • Basic-Leucine Zipper Transcription Factors/metabolism
  • Cells, Cultured
  • Disease Models, Animal
  • Genes, BRCA1
  • Ligands
  • Mammary Neoplasms, Experimental/genetics
  • Mammary Neoplasms, Experimental/metabolism
  • Mutant Proteins/chemistry
  • Mutant Proteins/genetics
  • Mutant Proteins/metabolism
  • Pancreatic Neoplasms/genetics
  • Pancreatic Neoplasms/metabolism
  • Phosphoproteins/metabolism
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Multimerization
  • RING Finger Domains
  • Tumor Suppressor Proteins/chemistry
  • Ubiquitin-Protein Ligases/chemistry
Strain Development
The targeting construct was electroporated into 129/Sv embryonic stem cells; exact genetic origin is unknown. Two independent neomycin-resistant ES clones (genotyped via sequencing) were injected into C57BL/6J blastocysts. Germline-transformed Brca1FH/+ heterozygous mice were mated with unspecified Flpe mice to remove the FRT-Hygo-FRT cassette. The offspring were backcrossed to C57BL/6J for 4 generations. Importation to MMRRC/JAX bred to C57BL/6J, but background analysis revealed the presence of 129 substrain components at seven separate markers. The line is, hence, deemed stock (listed as STOCK even though inbreeding to F20 has not ocurred).
Suggested Control Mice
wild-type
MMRRC Genetic QC Summary
The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact csmmrrc@jax.org. Older strains may not have this information.
Donor
Richard Baer, Ph.D., Columbia University Medical Center.
Primary Reference

Reid LJ, Shakya R, Modi AP, Lokshin M, Cheng JT, Jasin M, Baer R, Ludwig T. E3 ligase activity of BRCA1 is not essential for mammalian cell viability or homology-directed repair of double-strand DNA breaks. Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20876-81. doi: 10.1073/pnas.0811203106. Epub 2008 Dec 16. (Medline PMID: 19088202)

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)

Colony and Husbandry Information

Cryo-recovered strains distributed by the MMRRC at JAX are shipped to the customer from the Pathogen & Opportunistic-Free Animal Room G200 - see https://www.jax.org/jax-mice-and-services/customer-support/customer-service/animal-health/health-status-reports.

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email csmmrrc@jax.org.
Coat Color
Black
Eye
Black
MMRRC Breeding System
Backcross and sib-mating
Generation
N5 (C57BL/6J), F?
Overall Breeding Performance
Good
Viability and Fertility: Female Male Comments
Homozygotes are viable: Yes Yes
Homozygotes are fertile: Yes Yes
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: Undetermined Undetermined
Bred to Homozygosity
Yes
Average litter size
7 to 9
Recommended wean age
3 Weeks
Average Pups Weaned
7 to 9

Order Request Information

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 csmmrrc@jax.org 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.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description Distribution Fee / Unit (US $)
*Shipping & Handling not included*
Units Notes
069514-JAX-SPERM Cryo-preserved spermatozoa $437.00 / $437.00
Non-Profit / For-Profit
Aliquot Approximate quantity3
069514-JAX-RESUS Litter recovered from cryo-archive $2,022.00 / $2,022.00
Non-Profit / For-Profit
Litter Recovered litter4; additional fees for any special requests.
Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

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.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.