Strain Name:

C57BL/6J-Slc15a4m1Btlr/Mmjax

Availability:

Cryopreserved - Ready for recovery     Available at the JAX MMRRC

Please refer to the Mutant Mouse Regional Resource Center (MMRRC) for information about C57BL/6J-Slc15a4m1Btlr/Mmjax MMRRC Stock Number 034296.
Plasma dendritic cells from these ENU-induced Slc15a4 (feeble) mutant mice fail to produce IFN in response to challenge from CpG-A and TLR7 or TLR9 ligands. This mutant mouse strain may be useful in studies of toll like receptor signaling and plasmacytoid dendritic cell function in the immune system.

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Chemically Induced Mutation; Coisogenic; Mutant Strain;
Additional information on Genetically Engineered and Mutant Mice.
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Specieslaboratory mouse
GenerationF?pN1
Generation Definitions
 
Donating Investigator Bruce Beutler,   University of Texas Southwestern Medical

Description
Homozygotes: Mice that are homozygous for the mutation are viable and fertile. Although rare, plasmacytoid dendritic cells (pDCs) are responsible for most of the type 1 interferon (IFN) response following viral infection. pDCs from feeble mice fail to produce IFN in response to challenge from CpG-A and TLR7 or TLR9 ligands. In vitro challenge with TLR ligands abrogates secretion of IFN as well as that of other proinflammatory cytokines. In contrast, conventional dendritic cells from feeble mice produce a normal response to TLR ligands. This mutant mouse strain may be useful in studies of toll like receptor signaling and plasmacytoid dendritic cell function in the immune system.

Heterozygote: Not evaluated; heterozygote phenotype is expected to be normal.

Development
This missense point mutation was generated by ethylnitrosourea (ENU) mutagenesis in C57BL/6J males. Mutagenized males were outcrossed to C57BL/6J females. The mutation results aberrant splicing due to a T to A transversion in the intron 2 donor splice site. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Slc15a4m1Btlr/Slc15a4m1Btlr

        C57BL/6J-Slc15a4m1Btlr
  • immune system phenotype
  • abnormal interferon secretion
    • in vivo challenge with TLR7 or TLR9 ligands fails to produce type 1 interferon secretion in plasmacytoid dendritic cells; conventional dendritic cells respond normally to TLR ligands   (MGI Ref ID J:166600)
  • decreased interleukin-12 secretion
    • in vitro challenge with TLR7 or TLR9 ligands fails to produce IL12 secretion in plasmacytoid dendritic cells   (MGI Ref ID J:166600)
  • decreased interleukin-6 secretion
    • in vitro challenge with TLR7 or TLR9 ligands fails to produce IL6 secretion in plasmacytoid dendritic cells   (MGI Ref ID J:166600)
  • decreased tumor necrosis factor secretion
    • in vitro challenge with TLR7 or TLR9 ligands fails to produce TNFalpha secretion in plasmacytoid dendritic cells   (MGI Ref ID J:166600)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Immunology, Inflammation and Autoimmunity Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Slc15a4m1Btlr
Allele Name mutation 1, Bruce Beutler
Allele Type Chemically induced (ENU)
Common Name(s) feeble;
Mutation Made By Bruce Beutler,   University of Texas Southwestern Medical
Strain of OriginC57BL/6J
Gene Symbol and Name Slc15a4, solute carrier family 15, member 4
Chromosome 5
Gene Common Name(s) AA987064; AW742963; C130069N12Rik; PHT1; PTR4; RIKEN cDNA C130069N12 gene; expressed sequence AA987064; expressed sequence AW742963;
Molecular Note The feeble mutation has been identified as a T to A transversion in the intron 2 donor splice site. [MGI Ref ID J:166600] [MGI Ref ID J:86521]

Genotyping

Genotyping Information

Genotyping Protocols

Slc15a4m1Btlr, Pyrosequencing


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Blasius AL; Arnold CN; Georgel P; Rutschmann S; Xia Y; Lin P; Ross C; Li X; Smart NG; Beutler B. 2010. Slc15a4, AP-3, and Hermansky-Pudlak syndrome proteins are required for Toll-like receptor signaling in plasmacytoid dendritic cells. Proc Natl Acad Sci U S A 107(46):19973-8. [PubMed: 21045126]  [MGI Ref ID J:166600]

Additional References

Slc15a4m1Btlr related

Baccala R; Gonzalez-Quintial R; Blasius AL; Rimann I; Ozato K; Kono DH; Beutler B; Theofilopoulos AN. 2013. Essential requirement for IRF8 and SLC15A4 implicates plasmacytoid dendritic cells in the pathogenesis of lupus. Proc Natl Acad Sci U S A 110(8):2940-5. [PubMed: 23382217]  [MGI Ref ID J:194543]

Blasius AL; Krebs P; Sullivan BM; Oldstone MB; Popkin DL. 2012. Slc15a4, a gene required for pDC sensing of TLR ligands, is required to control persistent viral infection. PLoS Pathog 8(9):e1002915. [PubMed: 23028315]  [MGI Ref ID J:194867]

Hoebe K; Du X; Goode J; Mann N; Beutler B. 2003. Lps2: a new locus required for responses to lipopolysaccharide, revealed by germline mutagenesis and phenotypic screening. J Endotoxin Res 9(4):250-5. [PubMed: 12935356]  [MGI Ref ID J:86521]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryWhile maintaining a live colony, these mice are bred as homozygotes.

Pricing and Purchasing

Supply Notes


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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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