Overview

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.

Donating Investigator

Bruce Beutler, University of Texas Southwestern Medical

Genetic overview

Genetic Background	Generation

Slc15a4^m1Btlr

Allele Type	Gene Symbol	Gene Name
Chemically induced (ENU)	Slc15a4	solute carrier family 15, member 4

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Research Applications

Immunology, Inflammation and Autoimmunity Research

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Details

Detailed 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.

For additional information, see The Scripps Research Institute Mutagenix website.

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 Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

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):19973-8PubMed: 21045126 MGI: J:166600

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Genetics

Slc15a4^m1Btlr

Allele Symbol: Slc15a4^m1Btlr

Allele Name	mutation 1, Bruce Beutler
Allele Type	Chemically induced (ENU)
Allele Synonym(s)	feeble
Gene Symbol and Name	Slc15a4, solute carrier family 15, member 4
Gene Synonym(s)
Strain of Origin	C57BL/6J
Chromosome	5
Molecular Note	The feeble mutation has been identified as a T to A transversion in the intron 2 donor splice site.
Mutations Made By	Bruce Beutler, University of Texas Southwestern Medical

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Immunology, Inflammation and Autoimmunity Research

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Slc15a4^m1Btlr/Slc15a4^m1Btlr
C57BL/6J-Slc15a4

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

decreased interleukin-12 secretion
- in vitro challenge with TLR7 or TLR9 ligands fails to produce IL12 secretion in plasmacytoid dendritic cells

decreased interleukin-6 secretion
- in vitro challenge with TLR7 or TLR9 ligands fails to produce IL6 secretion in plasmacytoid dendritic cells

decreased tumor necrosis factor secretion
- in vitro challenge with TLR7 or TLR9 ligands fails to produce TNFalpha secretion in plasmacytoid dendritic cells

References

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):19973-8PubMed: 21045126 MGI: J:166600

Additional - Slc15a4^m1Btlr related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Pyrosequencing:Slc15a4
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, these mice are bred as homozygotes.
- Additional Breeding and Husbandry Support
Citation
When using the C57BL/6J-Slc15a4^m1Btlr/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #34296 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

The Jackson Laboratory's Genotype Promise

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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

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Questions about Terms of Use

Licensing Information

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Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Slc15a4m1Btlr

Allele Symbol: Slc15a4m1Btlr

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Slc15a4m1Btlr/Slc15a4m1BtlrC57BL/6J-Slc15a4

immune system phenotype

References

Additional - Slc15a4m1Btlr related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Slc15a4^m1Btlr

Allele Symbol: Slc15a4^m1Btlr

Genotype: Slc15a4^m1Btlr/Slc15a4^m1Btlr
C57BL/6J-Slc15a4

Additional - Slc15a4^m1Btlr related