Strain Name    : C57BL/6J-Flt3m1Btlr/Mmmh

Stock Number : 032824-MU

Gene Information

(provided by MGI)
Allele Symbol: Flt3m1Btlr
Name: mutation 1, Bruce Beutler
Chromosome: 5
Alteration at locus: Chemically Induced
Gene Symbol: Flt3
Name: FMS-like tyrosine kinase 3
Chromosome: 5
Alteration at locus: Chemically Induced
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:

ES Cell Line:

Additional mutations found on this strain:

AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00089:Flt3 APN 5 147354876 missense probably damaging 1.00
IGL01083:Flt3 APN 5 147354870 missense probably damaging 1.00
IGL01749:Flt3 APN 5 147358028 missense possibly damaging 0.94
IGL01765:Flt3 APN 5 147357978 missense probably benign 0.00
IGL02109:Flt3 APN 5 147350681 missense probably benign 0.00
IGL02490:Flt3 APN 5 147331296 missense probably damaging 1.00
IGL02631:Flt3 APN 5 147344552 missense probably damaging 1.00
R0070:Flt3 UTSW 5 147372726 splice acceptor site
R0070:Flt3 UTSW 5 147372726 splice acceptor site probably benign
R0320:Flt3 UTSW 5 147369579 splice acceptor site probably benign
R0347:Flt3 UTSW 5 147357992 missense probably damaging 1.00
R0512:Flt3 UTSW 5 147341270 nonsense probably null
R0968:Flt3 UTSW 5 147341227 missense possibly damaging 0.46
R1180:Flt3 UTSW 5 147341238 missense probably damaging 1.00
R1266:Flt3 UTSW 5 147356860 missense probably benign 0.00
R1562:Flt3 UTSW 5 147344513 missense probably damaging 1.00
R1705:Flt3 UTSW 5 147370593 splice acceptor site
R1803:Flt3 UTSW 5 147367055 nonsense probably null
R2000:Flt3 UTSW 5 147341238 missense probably damaging 1.00
R2021:Flt3 UTSW 5 147369490 missense probably damaging 0.98
R2079:Flt3 UTSW 5 147355083 missense probably damaging 0.97
R2261:Flt3 UTSW 5 147348063 missense probably benign 0.00
R2263:Flt3 UTSW 5 147348063 missense probably benign 0.00
R3087:Flt3 UTSW 5 147348046 missense probably benign 0.15
R3727:Flt3 UTSW 5 147354923 missense probably damaging 0.96
R3939:Flt3 UTSW 5 147356243 missense possibly damaging 0.94
X0018:Flt3 UTSW 5 147367066 missense possibly damaging 0.54

Phenotype

Homozygous phenotype: 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 phenotype: Wild type.

Mammalian Phenotype Terms:
Allelic Composition: Flt3m1Btlr/Flt3m1Btlr (Genetic Background: C57BL/6-Flt3m1Btlr )

Strain of Origin: C57BL/6J

Strain genetic background: C57BL/6J

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

  • Immunology and Inflammation
  • Research Tools
  • Virology

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

Random intra-strain mating.

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

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

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.
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 $)
Units Notes
032824-MU-RESUSLitter recovered from cryo-archive
$2,022.00
Non-Profit
Litter Recovered litter1; additional fees for any special requests.

1 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.

2 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.

3 An aliquot contains a sufficient number of embryos (in one or more vials and based on the transfer success rate of the MMRRC facility) to transfer to at least two recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

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 above). 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.



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.