Overview

Also Known As:TLR5^fl (TLR5 floxed exon 4)

The Tlr5^fl floxed allele has loxP sites flanking exon 4 of the toll-like receptor 5 gene. Cre recombinase-mediated removal of the floxed sequence creates a null allele. These mice may be useful in studying TLR5 recognition of pathogens (bacterial flagellin), cytokine secretion and activation of innate immune responses.
Of note, a C57BL/6-congenic TLR5 null allele (TLR5^-) is also available as Stock No. 028909.

Donating Investigator

Andrew T Gewirtz, Georgia State University

Benoit Chassaing, Georgia State University

Genetic overview

Genetic Background	Generation

Tlr5^tm1.1Gewr

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed))	Tlr5	toll-like receptor 5

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Research Applications

Research Tools
Immunology, Inflammation and Autoimmunity Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The Tlr5 gene encodes toll-like receptor 5, which has a fundamental role in bacteria recognition and activation of innate immune responses. TLR5 is the receptor for bacterial flagellin, and then acts via MYD88 and TRAF6; leading to NF-kappa-B activation, cytokine secretion and the inflammatory response.

The Tlr5^fl allele has loxP sites flanking exon 4 of the Tlr5 gene. Mice homozygous for the Tlr5^fl allele are viable and fertile with no reported abnormalities. When bred to mice that express Cre recombinase, the resulting offspring will have absence of Tlr5 function in cre-expressing tissues. Examples listed below.

When bred to germline Cre-expressing mice (Stock No. 006054), the resulting Tlr5 global knockout homozygotes are expected to exhibit increased levels of flagellated bacteria in the intestine, that will promote low-grade inflammation, metabolic syndrome and colitis.

When Tlr5^fl mice are bred to Villin-Cre transgenic mice (Stock No. 004586), the resulting Tlr5^ΔIEC homozygotes lack TLR5 expression in intestinal intraepithelial cells, and exhibit a phenotype similar to global TLR5 knockout mice.

When Tlr5^fl mice are bred to Cd11c-Cre transgenic mice (Stock No. 007567), the resulting Tlr5^ΔDC homozygotes lack TLR5 expression in dendritic cells, and exhibit complete loss of flagellin-induced production of interleukin-22, but do not develop an inflammation-associated phenotype or an altered microbiota composition, as seen in Tlr5^ΔIEC and in global TLR5 knockout mice.

Development

A targeting vector was designed by Dr. Andrew T. Gewirtz and Benoit Chassaing (Georgia State University) to have a loxP site upstream of exon 4, and a frt::loxP::Neo::frt::loxP cassette was inserted 211 base pairs downstream of exon 4 of the toll-like receptor 5 gene (Tlr5) on chromosome 1.

The construct was electroporated into the C57BL/6N-derived Ingenious Targeting Laboratory, Inc. embryonic stem (ES) cell line iTL IC1. Correctly targeted ES cells were injected into recipient blastocysts, and chimeric mice were bred with C57BL/6N to establish the colony.

Offspring were bred with C57BL/6-congenic Flp-expressing mice for germline deletion of the neo cassette; leaving exon 4 flanked by loxP sites.

The resulting TLR5^fl mice were bred together for several generations (and the Flp-expressing transgene was removed). At least one generation of breeding to C57BL/6J also occurred in 2012. In 2016, black homozygous males were sent to The Jackson Laboratory Repository (see SNP results below).

Upon arrival, sperm was cryopreserved. To establish our live colony in 2016, an aliquot of frozen sperm was used to fertilize C57BL/6NJ oocytes (Stock No. 005304).

In 2016, a 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the males sent to The Jackson Laboratory Repository and a cohort of first generation rederived living mice. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 5 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating in some mice. These data suggest that the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J;C57BL/6N genetic background (mostly C57BL/6J).

Control Suggestions

Approximate Controls

Additional Information

Considerations for Choosing Controls

Selected References

Chassaing B; Ley RE; Gewirtz AT. 2014. Intestinal epithelial cell toll-like receptor 5 regulates the intestinal microbiota to prevent low-grade inflammation and metabolic syndrome in mice. Gastroenterology 147(6):1363-77.e17PubMed: 25172014 MGI: J:229155

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Genetics

Tlr5^tm1.1Gewr

Allele Symbol: Tlr5^tm1.1Gewr

Allele Name	targeted mutation 1.1, Andrew Gewirtz
Allele Type	Targeted (Conditional ready (e.g. floxed))
Allele Synonym(s)	Tlr5^flox
Gene Symbol and Name	Tlr5, toll-like receptor 5
Gene Synonym(s)
Strain of Origin	C57BL/6NTac
Chromosome	1
Molecular Note	A targeting vector was designed to place a loxP site upstream of exon 4, and a frt::loxP::Neo::frt::loxP cassette inserted 211 base pairs downstream of exon 4. Flp-mediated recombination removed the FRT-flanked neo cassette leaving exon 4 floxed.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Research Tools
- Genetics Research
  - Mutagenesis and Transgenesis: Cre-lox System
  - Tissue/Cell Markers: Cre-lox System
- Infectious Disease
- Immunology, Inflammation and Autoimmunity Research
  - genes regulating susceptibility to infectious disease and endotoxin
- Cre-lox System
  - loxP-flanked Sequences
- Developmental Biology Research
  - Cre-lox System
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - multiple immune defects
  - Inflammatory bowel disease
  - Tlr deficiency
- Inflammation
  - Tlr deficiency
- CD Antigens, Antigen Receptors, and Histocompatibility Markers
  - genes regulating susceptibility to infectious disease and endotoxin
  - Tlr deficiency
- Growth Factors/Receptors/Cytokines
- Intracellular Signaling Molecules

Mammalian Phenotype Terms by Genotype

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

Genotype: Tlr5^tm1.1Gewr/Tlr5^tm1.1Gewr Tg(Itgax-cre,-EGFP)4097Ach/?
involves: C57BL/6J * C57BL/6NTac

adipose tissue phenotype

decreased total fat pad weight

digestive/alimentary phenotype

abnormal gut flora balance
- decreased distance of fecal bacteria from intestinal epithelial cells
- delayed clearance of pathobiont bacteria

mammalian phenotype

immune system phenotype
- Normal - mice do not exhibit spontaneous colitis, low grade inflammation or metabolic syndrome

Genotype: Tg(Vil1-cre)997Gum/? Tlr5^tm1.1Gewr/Tlr5^tm1.1Gewr
involves: C57BL/6J * C57BL/6NTac * SJL/J

adipose tissue phenotype

increased total fat pad weight
- increased adiposity on chow and high fat diet

growth/size/body region phenotype

enlarged spleen
- mild splenomegaly on chow and high fat diet

increased body weight
- on chow and high fat diet

hematopoietic system phenotype

enlarged spleen
- mild splenomegaly on chow and high fat diet

homeostasis/metabolism phenotype

increased circulating cholesterol level
- in males

increased circulating triglyceride level
- in males

increased fasting circulating glucose level
- high fat diet compounds hyperglycemia especially in female mice
- increased levels of blood glucose in males following 15 hr fast

behavior/neurological phenotype

polyphagia

immune system phenotype

enlarged spleen
- mild splenomegaly on chow and high fat diet

increased interleukin-1 beta secretion
- increased levels of colonic IL1B secretion in males treated with DSS

increased susceptibility to colitis induced morbidity/mortality
- increased mortality observed in mice on low dose DSS

large intestinal inflammation
- low grade inflammation, however mice do not develop spontaneous colitis

mortality/aging

increased susceptibility to colitis induced morbidity/mortality
- increased mortality observed in mice on low dose DSS

digestive/alimentary phenotype

abnormal colon morphology
- increased colon weight on high fat diet, length is similar to wild-type
- shorter and heavier colons on chow diet

abnormal gut flora balance
- alteration in microbiota composition as compared to controls
- decreased distance of bacteria from intestinal epithelial cells
- delayed clearance of pathobiont bacteria
- increase in levels of bacteria adherent to the colonic mucosa
- increase in levels of fecal bacteria

decreased colon length

increased susceptibility to colitis induced morbidity/mortality
- increased mortality observed in mice on low dose DSS

large intestinal inflammation
- low grade inflammation, however mice do not develop spontaneous colitis

References

Chassaing B; Ley RE; Gewirtz AT. 2014. Intestinal epithelial cell toll-like receptor 5 regulates the intestinal microbiota to prevent low-grade inflammation and metabolic syndrome in mice. Gastroenterology 147(6):1363-77.e17PubMed: 25172014 MGI: J:229155

Additional - Tlr5^tm1.1Gewr related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Tlr5
- Standard PCR:Tlr5 alternate1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, homozygous mice may be bred together.
- Additional Breeding and Husbandry Support
Citation
When using the TLR5^fl (TLR5 floxed exon 4) mouse strain in a publication, please cite the originating article(s) and include JAX stock #028599 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/Product	Description	Price
	Heterozygous for Tlr5<tm1.1Gewr>

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Frozen Mouse Embryo	B6(Cg)-Tlr5<tm1.1Gewr>/J	$2595.00
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Frozen Mouse Embryo	B6(Cg)-Tlr5<tm1.1Gewr>/J	$3373.50
Frozen Mouse Embryo	B6(Cg)-Tlr5<tm1.1Gewr>/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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Also Known As:TLR5fl (TLR5 floxed exon 4)

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Tlr5tm1.1Gewr

Allele Symbol: Tlr5tm1.1Gewr

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Tlr5tm1.1Gewr/Tlr5tm1.1Gewr Tg(Itgax-cre,-EGFP)4097Ach/?involves: C57BL/6J * C57BL/6NTac

adipose tissue phenotype

digestive/alimentary phenotype

mammalian phenotype

Genotype: Tg(Vil1-cre)997Gum/? Tlr5tm1.1Gewr/Tlr5tm1.1Gewrinvolves: C57BL/6J * C57BL/6NTac * SJL/J

adipose tissue phenotype

growth/size/body region phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

behavior/neurological phenotype

immune system phenotype

mortality/aging

digestive/alimentary phenotype

References

Additional - Tlr5tm1.1Gewr 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

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:TLR5^fl (TLR5 floxed exon 4)

Tlr5^tm1.1Gewr

Allele Symbol: Tlr5^tm1.1Gewr

Genotype: Tlr5^tm1.1Gewr/Tlr5^tm1.1Gewr Tg(Itgax-cre,-EGFP)4097Ach/?
involves: C57BL/6J * C57BL/6NTac

Genotype: Tg(Vil1-cre)997Gum/? Tlr5^tm1.1Gewr/Tlr5^tm1.1Gewr
involves: C57BL/6J * C57BL/6NTac * SJL/J

Additional - Tlr5^tm1.1Gewr related