Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tlr9tm1Aki mutation
(7 available);
any
Tlr9 mutation
(65 available)
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immune system
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• response to LPS and CpG is completely abrogated
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• no NK cell activation is observed following infection with L. infantum
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• following infection with Leishmania baziliensis
• however, secretion could be restored by treatment with GU-rich ssRNA, a TLR7 ligand
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• following infection with Leishmania baziliensis
• however, secretion could be restored by treatment with GU-rich ssRNA, a TLR7 ligand
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• following infection with attenuated yellow fever vaccine 17D (YF-17D), dendritic cells produce less IL-12p40 relative to wild-type mice
(J:118954)
• unlike in wild-type mice, IL-12p40 production from dendritic cells following infection with Leishmania infantum is indetectable
(J:125611)
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• following treatment with PbA(Plasmodium bergbei ANKA)-parasitized erythrocytes or LPS-stimulation, TNF secretion is reduced
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• myelin oligodendrocyte glycoprotein injection results in delayed onset of disease, 17.9 days after injection rather than 15.9 days as in controls
• fewer infiltrating foci in the spinal cord
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• following treatment with PbA (Plasmodium bergbei ANKA)-parasitized erythrocytes, mice have a partially decreased immune response in terms of TNF secretion and response to CpG
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• resistant to cerebral malaria
• reduced accumulation of hemozoin
• less upregulation of TNF-alpha in Plasmodium infection
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hematopoietic system
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• no NK cell activation is observed following infection with L. infantum
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tlr9tm1Aki mutation
(7 available);
any
Tlr9 mutation
(65 available)
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immune system
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• CpG-treated mice exhibit reduced Ly6Chi monocyte emigration from the bone marrow compared with similarly treated wild-type mice
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cellular
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• CpG-treated mice exhibit reduced Ly6Chi monocyte emigration from the bone marrow compared with similarly treated wild-type mice
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hematopoietic system
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• CpG-treated mice exhibit reduced Ly6Chi monocyte emigration from the bone marrow compared with similarly treated wild-type mice
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Allelic
Composition |
Tlr9tm1Aki/Tlr9tm1Aki
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Genetic
Background |
involves: 129P2/OlaHsd * BALB/c * C57BL/6 |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tlr9tm1Aki mutation
(7 available);
any
Tlr9 mutation
(65 available)
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immune system
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• failed to produce IFN-gamma in response to HSV-1 in vitro, but ability to control HSV-1 replication in vivo comparable to wild-type mice
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tlr9tm1Aki mutation
(7 available);
any
Tlr9 mutation
(65 available)
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immune system
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N |
• normal lymphocyte composition, as assessed by flow cytometry
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• impaired MHC class II expression in response to CpG DNA
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• no observed CpG-DNA-induced Th1-like response in vivo
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• impaired ability to produce IL6, IL12 and TNF-alpha in response to CpG DNA
(J:66049)
• production of IL6, IL12, and TNF-alpha in response to LPS, PGN, lipoprotein from Escherichia coli, zymosan, and heat-killed Staphylococcus aureus was comparable to wild-type controls
(J:66049)
• response to CpG is considerably decreased compared to wild-type
(J:117688)
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• impaired production of IL12 in response to CpG DNA, but not LPS
• impaired expression of CD40, CD80, CD86, and MHC II in response to CpG DNA, but not LPS
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• resistant to CpG-DNA-induced shock syndrome compared to wild-type mice
• unlike wild-type controls, no increase in serum IL6, IL12, or TNF-alpha in response to CpG-DNA in vivo
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hematopoietic system
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• impaired MHC class II expression in response to CpG DNA
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• no observed CpG-DNA-induced Th1-like response in vivo
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• impaired ability to produce IL6, IL12 and TNF-alpha in response to CpG DNA
(J:66049)
• production of IL6, IL12, and TNF-alpha in response to LPS, PGN, lipoprotein from Escherichia coli, zymosan, and heat-killed Staphylococcus aureus was comparable to wild-type controls
(J:66049)
• response to CpG is considerably decreased compared to wild-type
(J:117688)
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mortality/aging
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• 66% survival at 24 weeks
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hematopoietic system
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• spleens are 5-fold heavier than in MRL/MpJ-Faslpr mice
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• dramatically increased compared to wild-type; increased relative to Tlr9 and Fas mutants
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• total levels are higher than wild-type or Faslpr mice
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• lower than in Faslpr mice
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immune system
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• spleens are 5-fold heavier than in MRL/MpJ-Faslpr mice
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• dramatically increased compared to wild-type; increased relative to Tlr9 and Fas mutants
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• total levels are higher than wild-type or Faslpr mice
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• lower than in Faslpr mice
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• generalized lymphadenopathy
• axillary and inguinal lymph node weights are greater than in Faslpr mice (by >5-fold)
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• autoantibodies such as anti-ssDNA, anti-dsDNA, anti-cardiolipin, and anti-IgG are detected, and levels are not different from Fas mutants
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• interstitial lymphoid infiltration is observed at 13 weeks
• mesangial proliferation is greater than in Fas single mutants
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homeostasis/metabolism
renal/urinary system
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• increased more from 13 to 24 weeks than in Fas single mutants but not significantly so
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• interstitial lymphoid infiltration is observed at 13 weeks
• mesangial proliferation is greater than in Fas single mutants
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• glomerular IgG deposits that are exclusively mesangial are more severe than in Fas single mutants
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growth/size/body
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• spleens are 5-fold heavier than in MRL/MpJ-Faslpr mice
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immune system
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N |
• unlike in Smcr8em1Btlr homozygotes, spleen and lymph nodes are restored to normal as well as is the hyperactivation of T cells and increased circulating IL12p40 levels
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hematopoietic system
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• a 37% reduction in number of recirculating mature autoreactive B cells is observed compared to wild-type
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• more B1 cells are detected among peritoneal lymphocytes in double transgenic mutants compared to Tg(IghelMD4)4Ccg single transgenic mutants
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immune system
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• a 37% reduction in number of recirculating mature autoreactive B cells is observed compared to wild-type
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• more B1 cells are detected among peritoneal lymphocytes in double transgenic mutants compared to Tg(IghelMD4)4Ccg single transgenic mutants
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mortality/aging
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• as in Unc93b1tm1.1Kmiy homozygotes
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hematopoietic system
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• as in Unc93b1tm1.1Kmiy homozygotes
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mortality/aging
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• mutants show accelerated mortality relative to Faslpr homozygotes, with a median survival of 16.4 weeks compared to 25.1 weeks for Faslpr homozygotes
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immune system
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• splenomegaly is increased more than in Faslpr homozygotes
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• 3-fold increase in the number of CD4- CD8- double-negative T cells in the spleen compared to Faslpr homozygotes
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• increase in number of CD4+ helper T cells compared to Faslpr homozygotes
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• B cells have increased expression of activation markers CD44 and CD69 compared to Faslpr homozygotes, indicating increased B cell activation
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• increase in concentration of every IgG isotype compared to Faslpr homozygotes, with most prominent increases in IgG2a and IgG3
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• compared to Faslpr homozygotes
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• compared to Faslpr homozygotes
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• mice exhibit increased serum IFN-alpha concentration compared to Faslpr homozygotes
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• lymphadenopathy is increased more than in Faslpr homozygotes
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• splenic plasmacytoid dendritic cells (pDC) are more activated than those in single Faslpr homozygotes based on increased expression of MHC class II
• plasmacytoid DCs have an increased expression of the activation markers CD80 and CD86 compared to Faslpr homozygotes
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• mutants exhibit an increase in the incidence and severity of autoimmune skin disease compared to single Faslpr homozygous littermates
• mutants develop exacerbated kidney disease (lupus nephritis) compared to single Faslpr homozygotes
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• mutants show impaired ability to generate antibodies to DNA antigens compared to single Faslpr homozygotes, however they do generate antibodies reacting with cytoplasmic antigens that may include RNA
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• mice exhibit an elevated baseline level of anti-Smith-ribonucleoprotein autoantibodies compared to single Faslpr homozygotes
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• mutants develop exacerbated kidney disease (lupus nephritis) compared to Faslpr homozygotes
• a trend towards increased severity of interstitial infiltrates compared to Faslpr homozygotes
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• increase in glomerular size, cellularity, and protein deposition in kidneys leading to glomerulonephritis
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renal/urinary system
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• mutants develop exacerbated kidney disease (lupus nephritis) compared to Faslpr homozygotes
• a trend towards increased severity of interstitial infiltrates compared to Faslpr homozygotes
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• increase in glomerular size, cellularity, and protein deposition in kidneys leading to glomerulonephritis
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• glomerular size and cellularity are increased compared to Faslpr homozygotes
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hematopoietic system
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• splenomegaly is increased more than in Faslpr homozygotes
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• 3-fold increase in the number of CD4- CD8- double-negative T cells in the spleen compared to Faslpr homozygotes
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• increase in number of CD4+ helper T cells compared to Faslpr homozygotes
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• B cells have increased expression of activation markers CD44 and CD69 compared to Faslpr homozygotes, indicating increased B cell activation
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• increase in concentration of every IgG isotype compared to Faslpr homozygotes, with most prominent increases in IgG2a and IgG3
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• compared to Faslpr homozygotes
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• compared to Faslpr homozygotes
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homeostasis/metabolism
growth/size/body
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• splenomegaly is increased more than in Faslpr homozygotes
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Analysis Tools