Strain Detail Sheet

Strain Name:
C57BL/6J-Flt3m1Btlr/Mmmh
Stock Number:
032824-MU
Citation ID:
RRID:MMRRC_032824-MU
Major Collection:
Beutler Mutagenetix

Strain Information

Gene Details

Flt3m1Btlr
Name: FMS-like tyrosine kinase 3; mutation 1, Bruce Beutler
Synonyms: Flt3wmfl, warmflash
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 5
Alteration at locus: Chemically Induced
Flt3
Name: FMS-like tyrosine kinase 3
Synonyms: wmfl, Flk-2, Flk2, Flt-3, CD135
Type: Gene
Species: Mouse
Chromosome: 5
Alteration at locus: Chemically Induced
NCBI: 14255
HGNC: HGNC:3765
Homologene: 3040
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Genetic Alterations
G to A transition at position 33572 of the Flt3 genomic sequence (Genbank genomic region NC_000071 for linear genomic sequence of Flt3). The mutation destroys the donor site of intron 9, and results in the usage of an alternative donor site six nucleotides away in exon 9. This causes the in-frame deletion of the last two amino acids (YS) from exon 9.
Genotype Determination

Strain Description

Phenotype
Homozygous: The warmflash (wmfl) phenotype was identified among ENU-mutagenized G3 mice in a screen for susceptibility to mouse cytomegalovirus (MCMV). 100% of wmfl homozygotes died when infected with 2 x 10^5 pfu of MCMV, a normally sublethal inoculum. Five days after infection with 10^5 pfu of MCMV wmfl homozygotes showed increased viral titers in the spleen and liver comparable to those observed in BALB/c mice. 36 hours post-MCMV infection, exaggerated production of tumor necrosis factor (TNF)-? and IL-6 were noticeable in the serum of wmfl homozygotes, possibly driven by an increased viral load. In contrast, the level of interferon (IFN)-? was significantly reduced, and levels of interleukin (IL)-12 p70 and type I IFN were moderately but not significantly reduced in the serum of wmfl mice relative to those of WT control mice. The wmfl mutation did not impair virus recognition or alter TLR-mediated signaling in macrophages in vitro. Wmfl homozygotes also failed to control lymphocytic choriomeningitis virus (LCMV) (clone 13) infection.

Wmfl homozygotes have reduced numbers of natural killer (NK) cells and dendritic cells (DCs). Wmfl NK cells are intrinsically capable of acquiring full functionality in response to activating stimuli in vitro and in vivo. However, wmfl DCs produce reduced amounts of IL-12p40, type I IFN, and surface IL-15R? relative to WT DCs infected with MCMV or stimulated with TLR7 or TLR9 ligands. Co-culture experiments indicated that wmfl DC-mediated NK cell activation was impaired in response to TLR ligands and MCMV infection. Thus, the principal defect underlying MCMV susceptibility caused by the Flt3^wmfl mutation appears to be an impaired ability of DCs to assist in the activation of NK cells, which exist in diminished numbers in homozygous wmfl mice.

Wmfl DCs display a moderate defect, similar in magnitude to that of DCs from Unc93b1^3d/3d mice, in an in vivo assay for T cell proliferation dependent on cross- presentation by DCs.

The spleens and lymph nodes, but not thymi, of wmfl homozygotes were consistently smaller and showed reduced cellularity compared to those of control mice. Wmfl homozygotes were also slightly smaller than control mice of equivalent age and sex.

Heterozygous: Wild type.
Mammalian Phenotype Terms
Allelic Composition: Flt3m1Btlr/Flt3m1Btlr (Genetic Background: C57BL/6-Flt3m1Btlr )
MeSH Terms
  • Animals
  • Cell Survival
  • Cells, Cultured
  • Dendritic Cells/immunology
  • Herpesviridae Infections/immunology
  • Killer Cells, Natural/cytology
  • Killer Cells, Natural/immunology
  • Lymphocyte Activation
  • Mice
  • Muromegalovirus/immunology
  • Mutation
  • Signal Transduction
  • fms-Like Tyrosine Kinase 3/genetics
  • fms-Like Tyrosine Kinase 3/immunology
Strain Development
Original mutant was a C57BL/6J G3 ENU- induced mutant; all subsequent crosses to maintain strain were on C57BL/6J background only.
Suggested Control Mice

Wildtype littermates

MMRRC Genetic QC

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.

Research Applications

  • Immunology and Inflammation
  • Research Tools
  • Virology

Strain Origin

Donor
Bruce Beutler, M.D., The Scripps Research Institute
Primary Reference
  • Eidenschenk, C., Crozat, K., Krebs, P., Arens, R., Popkin, D., Arnold, C. N., Blasius, A. L., Benedict, C. A., Moresco, E. M. Y., Xia, Y., and Beutler, B. (2010) Flt3 Permits Survival during Infection by Rendering Dendritic Cells Competent to Activate NK Cells. Proc Natl Acad Sci U S A. 2010 May 25;107(21):9759-64. (Medline PMID: 20457904)
  • For additional information see: Mutagenetix, a catalog of mutations identified in the Beutler Laboratory at The Scripps Research Institute.

Colony and Husbandry Information

Special Considerations

Random intra-strain mating.

Health Status Report

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.

Order Request Information

Availability Level

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.

Conditions of Distribution

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.

The donor or their institution limits the distribution to non-profit institutions only.

Fees

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
032824-MU-RESUS Litter recovered from cryo-archive $5,475.00 / Non-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.