Overview

Also Known As: TLR3^-

Macrophages derived from these C57BL/6 background toll-like receptor 3 (Tlr3) targeted mutation animals fail to produce inflammatory cytokines, IFN-alpha or IFN-beta when challenged with poly(I:C), polyinosine-polycytidylic acid, a synthetic dsRNA analog. This mutant mouse strain may be useful in studies of the toll-like receptor pathway of the innate immune response.

Donating Investigator

Dr. Richard A. Flavell, Yale University School of Medicine

Genetic overview

Genetic Background	Generation
	N11+N1F6 (2019-03-18 00:00:00)

Tlr3^tm1Flv

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

View Genetics

Research Applications

Immunology, Inflammation and Autoimmunity Research
Cell Biology Research

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Base Price

Starting at:

$236.78 Domestic price for female 4-week

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Details

Detailed Description

Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Northern blot analysis detects a truncated gene product (mRNA), which is not functional. Unlike wildtype macrophages, macrophages derived from these animals fail to produce inflammatory cytokines, IFN-alpha or IFN-beta when challenged with poly(I:C), polyinosine-polycytidylic acid, a synthetic dsRNA analog. Splenocytes isolated from homozygotes do not respond to viral dsRNA and have diminished IL-6 production. Mice homozygous for the mutation are resistant to poly(I:C) induced shock and produce lower levels of IL-12. This mutant mouse strain may be useful in studies of the toll-like receptor pathway of the innate immune response.

Development

A targeting vector 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-Oca2⁺ Tyr⁺ Kitl^Sl-J derived W9.5 embryonic stem (ES) cells. This strain was backcrossed to C57BL/6 from the National Cancer Institute (NCI) ten times by the donating laboratory.

Control Suggestions

005304 C57BL/6NJ

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

View All References

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
  - Tlr deficiency
  - genes regulating susceptibility to infectious disease and endotoxin
- Immunodeficiency Associated with Other Defects
Cell Biology Research
- Signal Transduction

Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - Tlr deficiency
- CD Antigens, Antigen Receptors, and Histocompatibility Markers
  - Tlr deficiency
- Inflammation
  - Tlr deficiency

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
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

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

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
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 References

Li D; Wang W; Wu Y; Ma X; Zhou W; Lai Y. 2019. Lipopeptide 78 from Staphylococcus epidermidis Activates beta-Catenin To Inhibit Skin Inflammation. J Immunol 202(4):1219-1228PubMed: 30642981 MGI: J:272923

Additional - Tlr3^tm1Flv related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR:Tlr3^tm1Flv
- Genotyping resources and troubleshooting
Dietary Information
- New Diet as of March 2015: Lab Diet® 5K0Q (6% fat)
Breeding Considerations

When maintained as a live colony, homozygotes may be bred.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Homozygote
Citation
When using the TLR3^- mouse strain in a publication, please cite the originating article(s) and include JAX stock #009675 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX10 (Standard)

Pricing & Availability

Available

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	B6N.129S1-Tlr3<tm1Flv>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6N.129S1-Tlr3<tm1Flv>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6N.129S1-Tlr3<tm1Flv>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6N.129S1-Tlr3<tm1Flv>/J Frozen Embryo	$3373.50

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Also Known As: TLR3-

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/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/Tlr3tm1Flvinvolves: C57BL/6

hematopoietic system phenotype

immune system phenotype

mammalian phenotype

Genotype: Tlr3tm1Flv/Tlr3tm1FlvB6.129S1-Tlr3

behavior/neurological phenotype

neoplasm

nervous system phenotype

respiratory system phenotype

homeostasis/metabolism phenotype

immune system phenotype

References

Additional References

Additional - Tlr3tm1Flv related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

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

Also Known As: TLR3^-

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
Not Specified

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

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

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

Additional - Tlr3^tm1Flv related