Strain Name:
STOCK Bard1tm2.1Rjbr/Mmmh
Stock Number:
069510-MU
Citation ID:
RRID:MMRRC_069510-MU
Other Names:
Bard1 K607A

Strain Information

Bard1tm2.1Rjbr
Name: BRCA1 associated RING domain 1; targeted mutation 2.1, Richard J Baer
Synonyms: Bard1K607A, Bard1KA
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 1
Alteration at locus: Knock-In
Bard1
Name: BRCA1 associated RING domain 1
Synonyms: ENSMUSG00000073653, ENSMUSG00000060893
Type: Gene
Species: Mouse
Chromosome: 1
Alteration at locus: Knock-In
NCBI: 12021
HGNC: HGNC:952
Homologene: 400
Genetic Alterations
A nucleic acid alteration was introduced, predicting an amino acid change at codon 607, substituting lysine with alanine. This mutation disrupts the phosphate-binding pocket of the Bard1 BRCT domain and thereby abrogates the interaction between Bard1 and poly(ADP-ribose).
HVGS Nomenclature
  • Genbank RefSeq - mRNA: NM_007525.3
  • Genbank RefSeq, protein: NP_031551.1
  • Variant, nucleic acid level: c.1819_1820delinsGC
  • Variant, amino acid level, predicted: p.Lys607Ala (K607A)
  • Check this variant: LUMC Mutalyzer
ES Cell Line
KV1
Phenotype
The Bard1-K607A mutation abrogates the interaction of BARD1 with poly(ADP-ribose). Since this interaction is required for recruitment of the Brca1/Bard1 heterodimer to stalled replication forks, the Bard-K607A mutation ablates Brca1/Bard1 recruitment to stalled replication forks, resulting in fork degradation and chromosomal instability. Bard1-K607A acts as a “separation-of-function” mutation by disrupting the stalled-fork protection (SFP), but not the homology-directed repair (HDR), function of the Brca1/Bard1 heterodimer. Homozygous Bard1K607A/K607A mice display male infertility due to arrested spermatogenesis, but otherwise develop normally and do not exhibit increased tumor susceptibility.
MeSH Terms
  • Animals
  • BRCA1 Protein
  • Chromosomal Instability/genetics
  • DNA Breaks, Double-Stranded
  • DNA Repair/genetics
  • Female
  • Humans
  • Mice
  • Mutation
  • Protein Domains/genetics
  • Recombinational DNA Repair/genetics
  • Tumor Suppressor Proteins/genetics
  • Ubiquitin-Protein Ligases/genetics
Strain Development

The targeting construct inserted a loxP-PGK-neo-loxP cassette and the K607A missense mutation into exons 8 and 9, respectively. KV1 ES derived from (C57BL/6J x 129S6/SvEvTac)F1 were electroporated, and neomycin-resistant ES clones were screened by sequence analysis. Two independent clones of Bard1K607A-neo/+ ES cells were injected into C57BL/6J blastocysts for the production of germline-transformed mice. To excise the loxP-PGK-neo-loxP cassette from the targeted alleles, chimeric male Bard1K607A-neo/+ mice were mated with females carrying a ubiquitously expressed Cre transgene (B6.FVB-Tg(EIIa-cre)C5379Lmgd/J - RRID:IMSR_JAX:003724). Heterozygous Bard1K607A/+ mice were backcrossed to C57BL/6J mice which suggest animals approximately 97% C57BL/6J, based on backcross generation N4 (which includes the Cre line mating).

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 mmrrc@missouri.edu. Older strains may not have this information.
Donor
Richard Baer, Ph.D., Columbia University Medical Center.
Primary Reference

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 and Husbandry Information

Colony Surveillance Program and Current Health 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 mmrrc@missouri.edu.
Coat Color
Black
Eye
Black
MMRRC Breeding System
Backross and sib-mating
Generation
N4 (C57BL/6J and two B6-congenic allele modifiers), F?
Overall Breeding Performance
Good
Viability and Fertility: Female Male Comments
Homozygotes are viable: Yes Yes
Homozygotes are fertile: Yes Sterile
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 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.

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
069510-MU-SPERM Cryo-preserved spermatozoa $437.00 / $817.00
Non-Profit / For-Profit
Aliquot Approximate quantity3
069510-MU-RESUS Litter recovered from cryo-archive $2,624.00 / $5,340.00
Non-Profit / For-Profit
Litter Recovered litter4; additional fees for any special requests.
Cryopreserved material may be available upon request, please inquire to mmrrc@missouri.edu 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.