Overview

Podocytes derived from homozygous mice of this strain fail to respond to viral dsRNA. This mutant mouse strain may be useful in studies of the toll-like receptor pathway of innate immune response.

Donating Investigator

Steven N. Emancipator, Case Western Reserve University

Genetic overview

Genetic Background	Generation

Tlr3^tm1Flv

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Tlr3	toll-like receptor 3

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Research Applications

Immunology, Inflammation and Autoimmunity Research
Research Tools
Internal/Organ Research
Cell Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The doublestranded RNA pathogen-associated molecular patterns (PAMPs) associated with viral infections (specifically replicating viruses) and with necrotic cells, are recognized by toll-like receptor 3 (TLR3), which then induces the activation of NF-kappaB and the production of type I interferons. These mice carry a targeted mutation of the Tlr3, toll-like receptor 3, gene, in which exon 1 is disrupted. Mice that are homozygous for the targeted mutation are viable and fertile. Northern blot analysis of homozygotes on the B6;129S1 background detects a truncated gene product (mRNA), which is not functional. Podocytes derived from homozygotes on the congenic BALB/cJ background do not respond to extracellular dsRNA and transfected dsRNA suppresses wound healing in an in vitro assay. During backcrossing, the Y chromosome may not have been fixed to the BALB/cJ genetic background.

Development

A targeting vector designed by Drs. Lena Alexopoulou in the laboratory of Richard Flavell (Yale University) containing a loxP site flanked neomycin resistance cassette and a herpes simplex virus thymidine kinase gene was used to disrupt exon 1. The construct was electroporated into 129S1/Sv-p⁺ Tyr⁺ Kitl^Sl-J derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric male mice were crossed to female C57BL/6 mice. Dr. Steven N. Emancipator (Case Western Reserve University) obtained these Stock No. 005217 and backcrossed the mice to BALB/cJ (Stock No. 000651) for 12 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to BALB/cJ (Stock No. 000651) at least once to establish the colony.

Control Suggestions

000651 BALB/cJ

Additional Information

Considerations for Choosing Controls

Selected References

Alexopoulou L; Holt AC; Medzhitov R; Flavell RA. 2001. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413(6857):732-8PubMed: 11607032 MGI: J:72167

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Genetics

Tlr3^tm1Flv

Allele Symbol: Tlr3^tm1Flv

Allele Name	targeted mutation 1, Richard A Flavell
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	targeted mutation 1, Richard A Flavell; Tlr3^tm1Flv
Gene Symbol and Name	Tlr3, toll-like receptor 3
Gene Synonym(s)	CD283; IIAE2; expressed sequence AI957183; AI957183
Strain of Origin	129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Chromosome	8
Molecular Note	The gene was disrupted by replacement of exon 1 with a floxed neo cassette via homologous recombination. Northern blot analysis detected a truncated transcript in mutant animals. The mutant transcript does not encode a functional protein.
Mutations Made By	Lena Alexopoulou, Centre d'Immunologie de Marseille-Luminy

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Genotype: Tlr3^tm1Flv related

Immunology, Inflammation and Autoimmunity Research
- CD Antigens, Antigen Receptors, and Histocompatibility Markers
  - genes regulating susceptibility to infectious disease and endotoxin
  - Tlr deficiency
- Immunodeficiency Associated with Other Defects
Cell Biology Research
- Signal Transduction

Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - genes regulating susceptibility to infectious disease and endotoxin
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency Associated with Other Defects
- CD Antigens, Antigen Receptors, and Histocompatibility Markers
  - Tlr deficiency
  - genes regulating susceptibility to infectious disease and endotoxin
Internal/Organ Research
- Wound Healing
  - delayed/impaired
Cell Biology Research
- Signal Transduction

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Tlr3^tm1Flv/Tlr3^tm1Flv
involves: 129S1/Sv * C57BL/6

behavior/neurological phenotype

abnormal emotion/affect behavior

abnormal fear-related response

abnormal learning/memory/conditioning

abnormal long term spatial reference memory
- retain memory of platform location in Morris maze tests up to 120 hours compared to 72 hours in controls

abnormal response to novel object
- increased interest in novel objects

abnormal spatial working memory
- enhanced working memory

decreased anxiety-related response
- in open field tests and elevated + mazes

decreased fear-related response
- less cued fear response to a tone

impaired coordination
- poorer rotarod performance and motor learning

increased fear-related response
- greater hippocampus dependent contextual fear response, freezing times

cardiovascular system phenotype

abnormal vascular wound healing
- protective effect of poly I:C on neointimal formation is lost

hematopoietic system phenotype

abnormal B cell physiology
- impaired expression of CD69 in response to viral genomic dsRNA from Type I Lang mammalian reovirus
- impaired expression of CD69, CD80, and CD86 in response to poly(I:C), but not LPS

abnormal macrophage physiology
- impaired ability to produce IL6, IL12 and TNF-alpha in response to poly(I:C), a synthetic dsRNA analogue
- production of IL6, IL12, and TNF-alpha in response to LPS, PGN, LTA, zymosan, mannan, or CpG DNA was comparable to wild-type controls

homeostasis/metabolism phenotype

abnormal vascular wound healing
- protective effect of poly I:C on neointimal formation is lost

immune system phenotype

abnormal B cell physiology
- impaired expression of CD69 in response to viral genomic dsRNA from Type I Lang mammalian reovirus
- impaired expression of CD69, CD80, and CD86 in response to poly(I:C), but not LPS

abnormal macrophage physiology
- impaired ability to produce IL6, IL12 and TNF-alpha in response to poly(I:C), a synthetic dsRNA analogue
- production of IL6, IL12, and TNF-alpha in response to LPS, PGN, LTA, zymosan, mannan, or CpG DNA was comparable to wild-type controls

decreased inflammatory response
- produced less IL12 after poly(I:C) i.p. injection
- resistant to poly(I:C)-induced shock compared to wild-type mice

mammalian phenotype

immune system phenotype
- Normal - normal expression of CD3, B220, CD4, and CD8 in thymocytes and splenocytes
- Normal - normal lymphocyte development

nervous system phenotype

abnormal dentate gyrus morphology
- increased in volume

abnormal hippocampus CA1 region morphology
- increased in volume

abnormal hippocampus development
- increased hippocampal neurogenesis

Genotype: Tlr3^tm1Flv/Tlr3^tm1Flv
involves: C57BL/6

hematopoietic system phenotype

abnormal macrophage physiology
- impaired ability to produce type I interferon and TNF-alpha in response to dsRNA, but not in response to LPS

immune system phenotype

abnormal macrophage physiology
- impaired ability to produce type I interferon and TNF-alpha in response to dsRNA, but not in response to LPS

mammalian phenotype

immune system phenotype
- Normal - upregulation of costimulatory molecules, CD40 and CD86, by peritoneal macrophages in response to dsRNA was preserved on this background

Genotype: Tlr3^tm1Flv/Tlr3^tm1Flv
Not Specified

hematopoietic system phenotype

abnormal NK cell physiology
- NK and NK-T cell activation is significantly lower compared to C57BL/6 wild-type controls during mouse cytomegalovirus infection, however this decrease is not as pronounced as in Tlr9^CpG1 or Myd88^tm1Aki homozygotes

abnormal NK T cell physiology
- NK and NK-T cell activation is significantly lower compared to C57BL/6 wild-type controls during mouse cytomegalovirus infection, however this decrease is not as pronounced as in Tlr9^CpG1 or Myd88^tm1Aki homozygotes

immune system phenotype

abnormal cytokine secretion
- type 1 IFN, IFNgamma and IL-12 p40 levels are decreased compared to C57BL/6 wild-type controls following sublethal viral infection, however this decrease is not as pronounced as in Myd88^tm1Aki homozygotes

abnormal NK cell physiology
- NK and NK-T cell activation is significantly lower compared to C57BL/6 wild-type controls during mouse cytomegalovirus infection, however this decrease is not as pronounced as in Tlr9^CpG1 or Myd88^tm1Aki homozygotes

abnormal NK T cell physiology
- NK and NK-T cell activation is significantly lower compared to C57BL/6 wild-type controls during mouse cytomegalovirus infection, however this decrease is not as pronounced as in Tlr9^CpG1 or Myd88^tm1Aki homozygotes

increased susceptibility to viral infection
- viral loads are significantly higher after mouse cytomegalovirus infection compared to C57BL/6 wild-type controls, however titers are not as high as in Tlr9^CpG1 or Myd88^tm1Aki homozygotes

Genotype: Tlr3^tm1Flv/Tlr3^tm1Flv
involves: 129S1/Sv

cardiovascular system phenotype

heart inflammation
- higher viral titers of Encephalomyocarditis virus in the hearts of homozygotes
- less mononuclear cell and T cell infiltration of the myocardium at 3 and 5 days after infection

immune system phenotype

abnormal cytokine level

abnormal interferon level
- IFN-beta expression is augmented 3 days after infection

abnormal interleukin level
- change in expression is due at least in part due to expression in myocytes
- expression of IL1beta is delayed until 5 days after infection

abnormal tumor necrosis factor level
- change in expression is due at least in part due to expression in myocyte
- expression is delayed until 5 days after infection

decreased susceptibility to viral infection
- mice infected with rabies virus exhibit improved survival compared with wild-type mice

decreased susceptibility to viral infection induced morbidity/mortality
- in mice infected with rabies virus

heart inflammation
- higher viral titers of Encephalomyocarditis virus in the hearts of homozygotes
- less mononuclear cell and T cell infiltration of the myocardium at 3 and 5 days after infection

increased susceptibility to viral infection induced morbidity/mortality
- decreased survival after infection with Encephalomyocarditis virus
- higher viral titers in the heart
- homozygote deaths continue for 141 days after infection while control and heterozygote deaths level off after 8-10 days
- severe decline in survival of both homozygotes and heterozygotes after 3 days

endocrine/exocrine gland phenotype

abnormal pancreatic beta cell physiology
- insulin content of beta cells is unaffected by ds RNA whereas content decreases
- isolated beta cells are resistant to apoptosis induced by dsRNA and IFN-gamma or induced by dsRNA and lipofectamine

abnormal pancreatic islet morphology

decreased pancreatic beta cell mass
- slightly decreased beta cell mass although the percent volume is increased

increased pancreatic islet number

mortality/aging

decreased susceptibility to viral infection induced morbidity/mortality
- in mice infected with rabies virus

increased susceptibility to viral infection induced morbidity/mortality
- decreased survival after infection with Encephalomyocarditis virus
- higher viral titers in the heart
- homozygote deaths continue for 141 days after infection while control and heterozygote deaths level off after 8-10 days
- severe decline in survival of both homozygotes and heterozygotes after 3 days

reproductive system phenotype

abnormal postimplantation uterine environment
- no placental necrosis, hemorrhage or edema after intraperitoneal injection of poly I:C
- trophoblast fails to secrete cytokines in response to intraperitoneal injection of poly I:C

abnormal pregnancy
- intraperitoneal injection of poly I:C fails to induce preterm delivery as it does in controls

homeostasis/metabolism phenotype

abnormal circulating protein level
- serum levels of cardiac troponin I are elevated indicating myocardial damage

abnormal cytokine level

abnormal interferon level
- IFN-beta expression is augmented 3 days after infection

abnormal interleukin level
- change in expression is due at least in part due to expression in myocytes
- expression of IL1beta is delayed until 5 days after infection

abnormal tumor necrosis factor level
- change in expression is due at least in part due to expression in myocyte
- expression is delayed until 5 days after infection

hyperglycemia
- higher glycemia in the fed state but normal glucose tolerance

Genotype: Tlr3^tm1Flv/Tlr3^tm1Flv
B6.129S1-Tlr3

behavior/neurological phenotype

altered righting response
- treatment of mice at 4 days of age has no effect on righting behavior at 9 days of age, unlike controls

neoplasm

increased tumor incidence
- implanted tumor cells grow larger than in controls

nervous system phenotype

abnormal axon morphology
- number of axons in L1-L5 dorsal roots is unaffected by poly I:C treatment, unlike controls

abnormal neuron physiology
- isolated E14 dorsal root ganglion neurons are resistant to poly I:C inhibition of neurite outgrowth

respiratory system phenotype

abnormal respiratory system physiology
- antibody to IL13 attenuates the mucus response to Respiratory syncytial virus
- increased mucus in the lungs 6 days after infection

homeostasis/metabolism phenotype

abnormal cytokine level
- reduced cytokine response 8 hours after poly I:C treatment as determined by TNF alpha, IL-6, IL12p40, and IFN-beta

abnormal interleukin level
- IL-13 is upregulated in the lungs after infection with Respiratory syncytial virus
- IL-5 is upregulated later in the infection response to Respiratory syncytial virus

delayed wound healing
- full wound closure around 14 days rather than 12 days as in controls
- reduced infiltration of neutrophiles at days 1 and 3 and of macrophage at days 3 and 6
- reduced presence of chemokines involved in leukocyte recruitment
- wound healing of full thickness circular skin opennings are markedly delayed

immune system phenotype

abnormal cytokine level
- reduced cytokine response 8 hours after poly I:C treatment as determined by TNF alpha, IL-6, IL12p40, and IFN-beta

abnormal interleukin level
- IL-13 is upregulated in the lungs after infection with Respiratory syncytial virus
- IL-5 is upregulated later in the infection response to Respiratory syncytial virus

decreased interferon-beta secretion
- in peritoneal macrophages stimulated with poly(I:C)

References

Alexopoulou L; Holt AC; Medzhitov R; Flavell RA. 2001. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413(6857):732-8PubMed: 11607032 MGI: J:72167

Additional - Tlr3^tm1Flv related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR:Tlr3^tm1Flv
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred as homozygotes.
- Additional Breeding and Husbandry Support
Citation
When using the C.129S1(B6)-Tlr3^tm1Flv/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #022459 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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous for Tlr3<tm1Flv>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

Related Products and Services

Frozen Mouse Embryo	C.129S1(B6)-Tlr3<tm1Flv>/J	$2595.00
Frozen Mouse Embryo	C.129S1(B6)-Tlr3<tm1Flv>/J	$2595.00
Frozen Mouse Embryo	C.129S1(B6)-Tlr3<tm1Flv>/J	$3373.50
Frozen Mouse Embryo	C.129S1(B6)-Tlr3<tm1Flv>/J	$3373.50

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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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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Tlr3tm1Flv

Allele Symbol: Tlr3tm1Flv

Disease Terms

Research Areas By Genotype

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

Genotype: Tlr3tm1Flv related

Mammalian Phenotype Terms by Genotype

Genotype: Tlr3tm1Flv/Tlr3tm1Flvinvolves: 129S1/Sv * C57BL/6

behavior/neurological phenotype

cardiovascular system phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

mammalian phenotype

nervous system phenotype

Genotype: Tlr3tm1Flv/Tlr3tm1Flvinvolves: C57BL/6

hematopoietic system phenotype

immune system phenotype

mammalian phenotype

Genotype: Tlr3tm1Flv/Tlr3tm1FlvNot Specified

hematopoietic system phenotype

immune system phenotype

Genotype: Tlr3tm1Flv/Tlr3tm1Flvinvolves: 129S1/Sv

cardiovascular system phenotype

immune system phenotype

endocrine/exocrine gland phenotype

mortality/aging

reproductive system phenotype

homeostasis/metabolism phenotype

Genotype: Tlr3tm1Flv/Tlr3tm1FlvB6.129S1-Tlr3

behavior/neurological phenotype

neoplasm

nervous system phenotype

respiratory system phenotype

homeostasis/metabolism phenotype

immune system phenotype

References

Additional - Tlr3tm1Flv related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Tlr3^tm1Flv

Allele Symbol: Tlr3^tm1Flv

Genotype: Tlr3^tm1Flv related

Genotype: Tlr3^tm1Flv/Tlr3^tm1Flv
involves: 129S1/Sv * C57BL/6

Genotype: Tlr3^tm1Flv/Tlr3^tm1Flv
involves: C57BL/6

Genotype: Tlr3^tm1Flv/Tlr3^tm1Flv
Not Specified

Genotype: Tlr3^tm1Flv/Tlr3^tm1Flv
involves: 129S1/Sv

Genotype: Tlr3^tm1Flv/Tlr3^tm1Flv
B6.129S1-Tlr3

Additional - Tlr3^tm1Flv related