Overview

Also Known As:IL-1R1 restore knock-in (IL-1R1^r)

The interleukin 1 type I receptor restore allele (IL-1R1^r) is a functional null prior to Cre recombinase exposure. These mice allow Cre recombinase-inducible restoration of functional IL-1R1 expression, and visualization of IL-1R1-expressing cells with concordant labeling of IL-1R1 mRNA (by tdTomato fluorescence) and protein (by 3xHA epitope). IL-1R1^r mice may be useful for studying cell-type-specific functions of IL-1R1 in neuroimmunity and neuroinflammation.

Donating Investigator

Ning Quan, The Ohio State University

Genetic overview

Genetic Background	Generation

Il1r1^tm1Quan

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), Reporter, Null/Knockout)	Il1r1	interleukin 1 receptor, type I

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Research Applications

Neurobiology Research
Immunology, Inflammation and Autoimmunity Research
Research Tools
Internal/Organ Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The interleukin 1 type I receptor restore allele (IL-1R1^r) has a floxed interfering DNA region (comprised of three disrupting elements) preventing transcription/translation of IL-1R1 prior to Cre recombinase exposure, and has sequences inserted in place of the endogenous stop codon that allow tracking of Cre recombinase-restored expression of IL-1R1 mRNA (tdTomato fluorescence) and protein (3xHA epitope).

Homozygous (IL-1R1^r/r) mice have no endogenous IL-1R1 mRNA expression in any tissues, and exhibit the expected IL-1R1 knockout phenotype (no IL-1-induced CNS effects). Specifically, intracerebroventricular injection of IL-1β into IL-1R1^r/r mice did not produce brain endothelial COX-2 expression, CNS leukocyte infiltration or global microglia activation.

Prior to exposure to Cre recombinase, no tdTomato fluorescence or 3xHA expression is detected in brain tissue of IL-1R1^r/r mice.

Following Cre recombinase exposure, the resulting IL-1R1 Restored allele (IL-1R1^R) expresses functional IL-1R1, with robust tdTomato fluorescence in the cytoplasm of IL-1R1 mRNA-producing cells and 3xHA epitope-tagged IL-1R1 protein anchored to the cell membrane in the same cells. The restored 3xHA epitope-tagged IL-1R1 protein is readily detected by IHC in the normal brain.

The donating investigator reports that IL-1R1^r/r mice are viable and fertile with normal lifespan and no other gross abnormalities.

Development

The interleukin 1 type I receptor restore allele (IL-1R1^r) was created in the laboratory of Dr. Ning Quan (The Ohio State University) by inserting two knock-in target sequences into the interleukin 1 receptor, type I gene (Il1r1; IL-1R1) on chromosome 1.

The floxed knock-in target I sequence (T1; interfering DNA region) was inserted between Il1r1 exon IX and exon X; it was composed of a loxP site, a mouse Engrailed-2 splice acceptor sequence (En2 SA), a destabilization domain (DD; encoding a peptide tag that would destabilize the IL-1R1 molecule), a 2xPolyA transcriptional STOP sequence, a neo cassette and a second loxP site.

The knock-in target II (T2) sequence was inserted in place of the Il1r1 stop codon in exon XI; it was composed of 3 hemagglutinin tags (3xHA), a STOP codon fluorescent protein, an internal ribosome entry site (IRES), a tdTomato fluorescent protein sequence, a single frt site and a STOP codon.

The targeting vector was electroporated into embryonic stem (ES) cells derived from a C57BL6/NTac male mouse. Correctly targeted ES cells were injected into recipient blastocysts, and chimeras were bred to C57BL/6NCrl mice to generate heterozygous mice (IL-1R1^r/+). Heterozygotes were then bred together to generate homozygous mice (IL-1R1^r/r). The IL-1R1^r colony was maintained on a C57BL/6NCrl genetic background by breeding homozygous mice together for several generations prior to sending black males to The Jackson Laboratory Repository in 2015.

Upon arrival, males were used to cryopreserve sperm. To establish the living IL-1R1^r mouse colony, an aliquot of the frozen sperm was used to fertilize oocytes from C57BL/6NJ inbred females (Stock No. 005304).

Expression Data

Expressed Gene	HA, influenza hemagglutinin,
Expressed Gene	RFP, Red Fluorescent Protein, coral
Expressed Gene	Il1r1, interleukin 1 receptor, type I, mouse, laboratory
Site of Expression	Hemagglutinin epitope tags (HA), tdTomato, and Il1r1 will be expressed in in the cytoplasm of IL-1R1 mRNA-producing cells following Cre recombinase exposure.

Control Suggestions

Approximate Controls

005304 C57BL/6NJ

Additional Information

Considerations for Choosing Controls

Selected References

Liu X; Yamashita T; Chen Q; Belevych N; Mckim DB; Tarr AJ; Coppola V; Nath N; Nemeth DP; Syed ZW; Sheridan JF; Godbout JP; Zuo J; Quan N. 2015. Interleukin 1 type 1 receptor restore: a genetic mouse model for studying interleukin 1 receptor-mediated effects in specific cell types. J Neurosci 35(7):2860-70PubMed: 25698726 MGI: J:219864

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Genetics

Il1r1^tm1Quan

Allele Symbol: Il1r1^tm1Quan

Allele Name	targeted mutation 1, Ning Quan
Allele Type	Targeted (Conditional ready (e.g. floxed), Reporter, Null/Knockout)
Allele Synonym(s)	IL-1R1^r
Gene Symbol and Name	Il1r1, interleukin 1 receptor, type I
Gene Synonym(s)
Expressed Gene	HA, influenza hemagglutinin,
Expressed Gene	RFP, Red Fluorescent Protein, coral
Expressed Gene	Il1r1, interleukin 1 receptor, type I, mouse, laboratory
Site of Expression	Hemagglutinin epitope tags (HA), tdTomato, and Il1r1 will be expressed in in the cytoplasm of IL-1R1 mRNA-producing cells following Cre recombinase exposure.
Strain of Origin	C57BL/6NTac
Chromosome	1
Molecular Note	The allele contains two knock-in sequences incorporated by two rounds of homologous recombineering. The floxed target I sequence is inserted between exon IX and exon X; it is composed of a loxP site, a mouse engrailed 2 splice acceptor sequence, a destabilization domain (DD), a 2xPolyA transcriptional STOP sequence, a neo cassette and a second loxP site.Target II sequence is inserted in place of the Il1r1 stop codon in exon XI; it is composed of 3 hemagglutinin tags (3xHA), a STOP codon fluorescent protein, an internal ribosome entry site (IRES), a tdTomato fluorescent protein sequence, a single FRT site and a STOP codon. Mice containing target I do not produce a functional protein.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Neurobiology Research
- Cre-lox System
  - loxP-flanked Sequences
  - loxP-flanked Sequences: Test/Reporter
- Fluorescent protein expression in neural tissue
- Neurodegeneration
- Behavioral and Learning Defects
- Receptor Defects
Immunology, Inflammation and Autoimmunity Research
- Intracellular Signaling Molecules
- CD Antigens, Antigen Receptors, and Histocompatibility Markers
  - genes regulating susceptibility to infectious disease and endotoxin
- Growth Factors/Receptors/Cytokines
Research Tools
- Neurobiology Research
  - cell marker
- Fluorescent Proteins
- Cre-lox System
  - loxP-flanked Sequences
  - loxP-flanked Sequences: Test/Reporter
- Genetics Research
  - Tissue/Cell Markers: neurons
Internal/Organ Research
- Wound Healing

Mammalian Phenotype Terms by Genotype

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

Genotype: Il1r1^tm1Quan/Il1r1^tm1Quan Tg(Tek-cre)12Flv/0
involves: C3H * C57BL/6

hematopoietic system phenotype

abnormal microglial cell activation
- microglia are activated (deramified) throughout the brain prenchyma following IL1beta injection

immune system phenotype

abnormal microglial cell activation
- microglia are activated (deramified) throughout the brain prenchyma following IL1beta injection

abnormal inflammatory response
- intracerebroventricular IL1beta administration results in leukocyte infiltration (CD45+ cell trafficking) to the brain parenchyma 12 hours after injection

nervous system phenotype

abnormal microglial cell activation
- microglia are activated (deramified) throughout the brain prenchyma following IL1beta injection

Genotype: Il1r1^tm1Quan/Il1r1^tm1Quan Lyz2^tm1(cre)Ifo/Lyz2^tm1(cre)Ifo
involves: 129P2/OlaHsd * C57BL/6

hematopoietic system phenotype

abnormal microglial cell activation
- microglia are only activated (deramified) in hippocampus region following IL1beta injection rather than throughout the brain parenchyma

immune system phenotype

abnormal inflammatory response
- intracerebroventricular IL1beta injection does not result in leukocyte infiltration to the brain parenchyma in contrast to wild-type controls

abnormal microglial cell activation
- microglia are only activated (deramified) in hippocampus region following IL1beta injection rather than throughout the brain parenchyma

nervous system phenotype

abnormal microglial cell activation
- microglia are only activated (deramified) in hippocampus region following IL1beta injection rather than throughout the brain parenchyma

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

Genotype: Il1r1^tm1Quan/Il1r1^tm1Quan
involves: C57BL/6

hematopoietic system phenotype

abnormal microglial cell activation
- microglia remain in unstimulated resting stage (ramified morphology) following IL1beta injection

immune system phenotype

abnormal microglial cell activation
- microglia remain in unstimulated resting stage (ramified morphology) following IL1beta injection

abnormal inflammatory response
- intracerebroventricular IL1beta injection does not result in leukocyte infiltration to the brain parenchyma in contrast to wild-type controls

nervous system phenotype

abnormal microglial cell activation
- microglia remain in unstimulated resting stage (ramified morphology) following IL1beta injection

References

Liu X; Yamashita T; Chen Q; Belevych N; Mckim DB; Tarr AJ; Coppola V; Nath N; Nemeth DP; Syed ZW; Sheridan JF; Godbout JP; Zuo J; Quan N. 2015. Interleukin 1 type 1 receptor restore: a genetic mouse model for studying interleukin 1 receptor-mediated effects in specific cell types. J Neurosci 35(7):2860-70PubMed: 25698726 MGI: J:219864

Additional - Il1r1^tm1Quan related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Il1r1 T1-alternate1
- Separated PCR:Il1r1 T2-alternate1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous mice may be bred together, to wildtype mice from the colony or to C57BL/6NJ inbred mice (Stock No. 005304). Alternatively, homozygous mice may be bred together.
- Additional Breeding and Husbandry Support
Mating System
- Heterozygote x Heterozygote
Citation
When using the IL-1R1 restore knock-in (IL-1R1^r) mouse strain in a publication, please cite the originating article(s) and include JAX stock #024101 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

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> >	Heterozygous for Il1r1<tm1Quan>

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Frozen Mouse Embryo	C57BL/6N-Il1r1<tm1Quan>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	C57BL/6N-Il1r1<tm1Quan>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	C57BL/6N-Il1r1<tm1Quan>/J Frozen Embryos	$3373.50
Frozen Mouse Embryo	C57BL/6N-Il1r1<tm1Quan>/J Frozen Embryos	$3373.50

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The Jackson Laboratory's Genotype Promise

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.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:IL-1R1 restore knock-in (IL-1R1r)

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Il1r1tm1Quan

Allele Symbol: Il1r1tm1Quan

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Il1r1tm1Quan/Il1r1tm1Quan Tg(Tek-cre)12Flv/0involves: C3H * C57BL/6

hematopoietic system phenotype

immune system phenotype

nervous system phenotype

Genotype: Il1r1tm1Quan/Il1r1tm1Quan Lyz2tm1(cre)Ifo/Lyz2tm1(cre)Ifoinvolves: 129P2/OlaHsd * C57BL/6

hematopoietic system phenotype

immune system phenotype

nervous system phenotype

Genotype: Il1r1tm1Quan/Il1r1tm1Quaninvolves: C57BL/6

hematopoietic system phenotype

immune system phenotype

nervous system phenotype

References

Additional - Il1r1tm1Quan related

Genotyping Protocols

Breeding Considerations

Mating System

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

Also Known As:IL-1R1 restore knock-in (IL-1R1^r)

Il1r1^tm1Quan

Allele Symbol: Il1r1^tm1Quan

Genotype: Il1r1^tm1Quan/Il1r1^tm1Quan Tg(Tek-cre)12Flv/0
involves: C3H * C57BL/6

Genotype: Il1r1^tm1Quan/Il1r1^tm1Quan Lyz2^tm1(cre)Ifo/Lyz2^tm1(cre)Ifo
involves: 129P2/OlaHsd * C57BL/6

Genotype: Il1r1^tm1Quan/Il1r1^tm1Quan
involves: C57BL/6

Additional - Il1r1^tm1Quan related