|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.|
Type Chemically Induced Mutation; Coisogenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation F?pN1
Donating Investigator Bruce Beutler, University of Texas Southwestern Medical
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.
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.
|Considerations for Choosing Controls|
View Mammalian Phenotype TermsMammalian Phenotype Terms provided by MGIassigned by genotype
- 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 ApplicationsResearch ApplicationsThis mouse can be used to support research in many areas including:
|Allele Name||mutation 1, Bruce Beutler|
|Allele Type||Chemically induced (ENU)|
|Mutation Made By||Bruce Beutler, University of Texas Southwestern Medical|
|Strain of Origin||C57BL/6J|
|Gene Symbol and Name||Slc15a4, solute carrier family 15, member 4|
|Gene Common Name(s)||AA987064; AW742963; C130069N12Rik; FP12591; 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]|
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]
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]
Animal Health ReportsProduction of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.
Breeding & Husbandry While maintaining a live colony, these mice are bred as homozygotes.
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