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Strain Name:
B6.Cg-Brd4tm1Dey/Mmucd
Stock Number:
076000-UCD
Citation ID:
RRID:MMRRC_076000-UCD
Other Names:
Brd4Fl/Fl

Strain Information

QUALITY CONTROL OF B6.Cg-Brd4tm1Dey/Mmucd  |  University of California at Davis
Last Updated:
Strain Data and Information Information by Submitter Assessed by MMRRC1,2
Published Provided
Allele-specific genotype3n.d.
Genetic backgroundn.d.
Viability of genotypes available for distribution n.d.
Specific Pathogen- Status n.d.
Recoverability of cryopreserved sperm/embryos4 n.d.
Gene or allele sequence3 n.d.
Gene or allele expression3n.d.
Gene or allele function3n.d.
Observable and/or measurable phenotypesn.d.
Fertility of genotypes available for distribution n.d.
Fecundity/breeding performance n.d.

1 When indicated as verified ("YES"), then please note that information presented is to the best of our knowledge correct and up-to-date at the time of verification at the MMRRC Distribution Center; however, this information is subject to change due to breeding, maintenance, and other actions on the mouse strain at the MMRRC Distribution Center; direct any questions on this table to the MMRRC Distribution Center for this mouse stain.

2 If verification has not been performed (as indicated by "NO"), investigators may request specific verification testing for a fee. Requests should be submitted directly to the MMRRC Distribution Center assigned to the management, archiving, and distribution of the strain. A full listing of available testing and analytical services is available at https://www.mmrrc.org/about/services.php.

3 This information may or may not apply to each individual engineered allele (e.g., Cre, FlpO) present in the strain.

4 Recovery refers to thawing, in vitro fertilization (IVF), and/or embryo culture leading to live offspring.

Brd4
Name: bromodomain containing 4
Synonyms: MCAP, HUNK1, WI-11513
Type: Gene
Species: Mouse
Chromosome: 17
NCBI: 57261
Homologene: 136213
Genetic Alterations
The endogenous exon 3 of the Brd4 locus, generated a conditional floxed allele (Brd4Fl). In the absence of Cre recombinase, Brd4 expression remains intact. Cre-mediated excision of exon 3 results in disruption of Brd4 and production of a null allele in targeted tissues.
ES Cell Line
R1 derived from (129X1/SvJ x 129S1/Sv)F1-Kitl+
Phenotype

Constitutive deletion of Brd4 results in severe defects in hematopoietic development.

  • Brd4 knockout embryos (Brd4Fl/Fl) are viable, fertile, and exhibit no gross morphological abnormalities under baseline conditions.
  • Cre-mediated Brd4Fl/Fl knockout embryos exhibit smaller than wild-type littermates and display pale fetal livers (consistent with impaired hematopoiesis).
    • Flow cytometric analysis of fetal liver cells demonstrates a reduction in the Lin⁻Sca1⁺cKit⁺ (LSK) compartment, including significant decreases in Flt3lo hematopoietic stem cells (HSCs) and Flt3hi multipotent progenitors (MPPs). Consequently, both myeloid and lymphoid lineage populations are diminished in knockout embryos.
    • In contrast, BRD4 deletion in differentiated macrophages partially affects inflammatory gene expression and proliferation, while preserving many macrophage functions.
  • Rare Brd4 knockout mice that survive to adulthood exhibit reduced myeloid and lymphoid cell populations in bone marrow and spleen, indicating a critical requirement for Brd4 in hematopoietic stem cell expansion and functional immune system development.
MeSH Terms
  • Animals
  • Biomarkers/analysis
  • Cells, Cultured
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Hematopoietic Stem Cells/cytology
  • Inflammation/chemically induced
  • Inflammation/genetics
  • Inflammation/immunology
  • Inflammation/pathology
  • Lipopolysaccharides/toxicity
  • Macrophages, Peritoneal/drug effects
  • Macrophages, Peritoneal/immunology
  • Macrophages, Peritoneal/metabolism
  • Macrophages, Peritoneal/pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nuclear Proteins/physiology
  • Transcription Factors/physiology
Strain GQC Summary
Gene Specific Genotyping:

To request gene-specific and other genotyping services for a strain, please contact the distribution MMRRC Center for more information.

Background Genetic Quality:

The MMRRC has developed a Genetic Quality Control pipeline using the MiniMUGA array to provide additional information to identify and validate genetic backgrounds of MMRRC strains. For more information on whether genetic background data is available, please contact MMRRC_GeneticQC@med.unc.edu. Note: that MiniMUGA genetic background data is not available on all strains, but can be ordered if desired.

Suggested Control Mice
Littermates of all relevant genotypes.
  • Cell Biology
  • Immunology and Inflammation
  • Neurobiology
Submitter
Anup Dey, Ph.D., National Institutes of Health (NIH).
Primary Reference

Dey A, Yang W, Gegonne A, Nishiyama A, Pan R, Yagi R, Grinberg A, Finkelman FD, Pfeifer K, Zhu J, Singer D, Zhu J, Ozato K. BRD4 directs hematopoietic stem cell development and modulates macrophage inflammatory responses. EMBO J. 2019 Apr 1;38(7):e100293. doi: 10.15252/embj.2018100293. Epub 2019 Mar 6. (Medline PMID: 30842097)

Strain Development

A ~20 kb targeting vector containing loxP sites flanking exon 3 of the Brd4 locus were introduced into 129Sv R1 embryonic stem cells by homologous recombination. The vector was transfected into murine 129 R1 ES cells (derived from the strain (129X1/SvJ x 129S1/Sv)F1-Kitl+). Correctly targeted ES cell clones were injected into blastocysts to generate chimeric mice. Germline-transmitting chimeras were bred with FLP recombinase-expressing mice to remove the neomycin resistance cassette, leaving exon 3 flanked by loxP sites.

Resultant Brd4Fl/+ mice were backcrossed to C57BL/6J mice for more than ten generations to establish a congenic B6 background (B6.C N>10). Homozygous Brd4Fl/Fl mice were maintained by sib-mating. Genotyping was performed by PCR to distinguish wild-type and floxed alleles.


Disclaimer: If MMRRC Strain Genetic Quality Control (GQC; based on MiniMUGA genotyping and analysis) has been completed for this strain, the information might differ from the genetic background information provided by the submitter. MiniMUGA genetic analysis is done on a strain’s tissue samples taken when archived by or ordered from the assigned MMRRC Center.

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@ucdavis.edu.
Coat Color
Black
Eye
Black
MMRRC Breeding System
Sib-mating
Generation
N>=10
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: 4 to 6 months 7 to 9 months
Average litter size
4 to 6
Recommended wean age
3 Weeks
Average Pups Weaned
4 to 6

Order Information

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

A Commercial License Agreement from the Submitter is required for for-profit entities to use this strain. For more information, please contact Nicole Guyton.

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 Submitter is required for for-profit entities to use this strain. For more information, please contact Nicole Guyton

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
076000-UCD-RESUS Litter recovered from cryo-archive $5,892.91 / $6,181.91
Non-Profit / For-Profit
Litter Recovered litter4; additional fees for any special requests.

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.