Allele Symbol: Flt3m1Btlr
Name: mutation 1, Bruce Beutler
Alteration at locus: Chemically Induced
Gene Symbol: Flt3
Name: FMS-like tyrosine kinase 3
Alteration at locus: Chemically Induced
ES Cell Line: Not Applicable
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.
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:
Donor: Bruce Beutler, M.D., The Scripps Research Institute
Random intra-strain mating.
Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.
Fee/unit (US $)
|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). 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.