Overview

Also Known As: Il1r1^-

IL-1 receptor KO mice exhibit altered innate immune and inflammatory responses and show multiple effects on physiological systems and behavior.

Donating Investigator

Dr. Jacques Peschon, Amgen

Genetic overview

Genetic Background	Generation
	N5+N3F8 (2018-04-02 00:00:00)

Il1r1^tm1Imx

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Il1r1	interleukin 1 receptor, type I

View Genetics

Research Applications

Cancer Research
Immunology, Inflammation and Autoimmunity Research

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Base Price

Starting at:

$224.00 Domestic price for female 5-week

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Details

Detailed Description

Interleukin 1 receptor, type I, is a receptor for interleukin 1 (IL1), which affects many cytokine induced immune and inflammatory responses. Mice homozygous for the Il1r^tm1Imx targeted mutation therefore fail to respond to IL1 and exhibit an altered immune response to many different target proteins. Some effects seen from knocking out this receptor include defective responses to certain inflammatory agents such as turpentine and altered response to various pathogenic organisms such as S. aureus and C. pneumoniae.

Other observed effects include enhanced glucose homeostasis, enhanced insulin sensitivity of adipose tissue, reduction in diet-induced systemic atherosclerosis, improved restoration of normal skin architecture in wounds, increased incidence of acute convulsive seizures induced by pentylenetetrazole, and a decrease in anxiety-related behaviors.

Development

A null mutation in Il1r1 was generated by homologous recombination in 129/SvEv AB1 ES cells using a replacement vector in which a 2.4 kb EcoR1-Pst1 fragment encompassing two exons was replaced with a PGKneo cassette. Targeted mutant mice were backcrossed 5 times to C57BL/6 prior to importation (see SNP note below).

A 48 SNP (single nucleotide polymorphism) panel analysis, with 43 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 rederived living colony at The Jackson Laboratory Repository. One the 43 markers on Chromosome 8 was segregating with 129. Also, 2 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Control Suggestions

000664 C57BL/6J, ()

Additional Information

Considerations for Choosing Controls

Selected References

Glaccum MB; Stocking KL; Charrier K; Smith JL; Willis CR; Maliszewski C ; Livingston DJ ; Peschon JJ ; Morrissey PJ. 1997. Phenotypic and functional characterization of mice that lack the type I receptor for IL-1. J Immunol 159(7):3364-71PubMed: 9317135 MGI: J:43088

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Genetics

Il1r1^tm1Imx

Allele Symbol: Il1r1^tm1Imx

Allele Name	targeted mutation 1, Immunex Research and Development Corporation
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	targeted mutation 1, Immunex Research and Development Corporation; Il1r1^tm1Imx
Gene Symbol and Name	Il1r1, interleukin 1 receptor, type I
Gene Synonym(s)	D2S1473; IL-iR; IL1R; IL-1R-alpha; IL-1R1; IL1RA; P80; Il1r-1; IL-1 receptor alpha chain; Il1r-1; CD121A; CD121a
Strain of Origin	129S7/SvEvBrd-Hprt⁺
Chromosome	1
Molecular Note	A neomycin resistance cassette replaced two exons of the gene, which encode amino acids 4 - 225 of the mature protein.
Mutations Made By	Dr. Jacques Peschon, Amgen

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Genotype: Il1r1^tm1Imx related

Cancer Research
- Growth Factors/Receptors/Cytokines
Immunology, Inflammation and Autoimmunity Research
- Growth Factors/Receptors/Cytokines

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^tm1Imx/Il1r1^tm1Imx
involves: 129 * C57BL/6

craniofacial phenotype

dental pulp necrosis
- complete necrosis of the dental pulp is observed by 21 days after inoculation compared to control mice that still have intact dental pulp at 38 days post-innoculation
- mice have significantly higher necrosis scores of the dental pulp seven days after bacterial inoculation

skeleton phenotype

dental pulp necrosis
- complete necrosis of the dental pulp is observed by 21 days after inoculation compared to control mice that still have intact dental pulp at 38 days post-innoculation
- mice have significantly higher necrosis scores of the dental pulp seven days after bacterial inoculation

increased bone resorption
- osteoclast activity of the molars is 2-fold higher than in wild-types 7 days after bacterial inoculation
- there is significantly more osteoclastogenesis that occurs in molars between 7 and 21 days after bacterial infection of the dental pulp

osteomyelitis
- osteolytic lesions of molars are significantly larger in these mice 2 weeks after bacterial inoculation of the dental pulp
- the osteolytic lesions continue to be larger for at least 38 days post inoculation

growth/size/body region phenotype

dental pulp necrosis
- complete necrosis of the dental pulp is observed by 21 days after inoculation compared to control mice that still have intact dental pulp at 38 days post-innoculation
- mice have significantly higher necrosis scores of the dental pulp seven days after bacterial inoculation

homeostasis/metabolism phenotype

decreased circulating interleukin-6 level
- no IL-6 is detected in sera of mice injected with IL-1alpha

immune system phenotype

decreased circulating interleukin-6 level
- no IL-6 is detected in sera of mice injected with IL-1alpha

increased susceptibility to bacterial infection
- mice have 3 log greater bacterial penetration of the dental pulp eight days after bacterial innoculation

osteomyelitis
- osteolytic lesions of molars are significantly larger in these mice 2 weeks after bacterial inoculation of the dental pulp
- the osteolytic lesions continue to be larger for at least 38 days post inoculation

Genotype: Il1r1^tm1Imx/Il1r1^tm1Imx
involves: 129S7/SvEvBrd

craniofacial phenotype

delayed tooth eruption
- mice exhibit delayed eruption of mandibular and maxillary incisors and molars compared with wild-type mice

growth/size/body region phenotype

delayed tooth eruption
- mice exhibit delayed eruption of mandibular and maxillary incisors and molars compared with wild-type mice

hematopoietic system phenotype

abnormal neutrophil physiology
- neutrophile response to monosodium urate injected into the peritoneal cavity is reduced 85% relative to controls

immune system phenotype

abnormal neutrophil physiology
- neutrophile response to monosodium urate injected into the peritoneal cavity is reduced 85% relative to controls

skeleton phenotype

delayed tooth eruption
- mice exhibit delayed eruption of mandibular and maxillary incisors and molars compared with wild-type mice

Genotype: Il1r1^tm1Imx/Il1r1^tm1Imx
involves: 129S7/SvEvBrd * C57BL/6

growth/size/body region phenotype

increased body weight
- in some experiments

immune system phenotype

abnormal neutrophil physiology
- following ischemic/reperfusion injury, mice exhibit reduced polymorphonuclear leukocyte infiltration compared with wild-type mice

decreased susceptibility to experimental autoimmune uveoretinitis
- following reverse passive Arthus reaction to induce uveitis, mice exhibit reduced cellular infiltration into the anterior and posterior segments compared with wild-type mice

renal/urinary system phenotype

decreased susceptibility to kidney reperfusion injury
- following ischemic/reperfusion injury, mice exhibit reduced blood urea nitrogen and creatinine levels at 48 and 72 hours with reduced polymorphonuclear leukocyte infiltration compared with wild-type mice
- Normal - however, tubular damage is normal

hematopoietic system phenotype

abnormal neutrophil physiology
- following ischemic/reperfusion injury, mice exhibit reduced polymorphonuclear leukocyte infiltration compared with wild-type mice

homeostasis/metabolism phenotype

abnormal response/metabolism to endogenous compounds
- Normal - however, behavioral response to LPS treatment is normal
- mice treated with IL1b, either intraperitoneally or intracerebroventricularly, fail to exhibit a decrease in social exploration, immobility, decrease in body weight, or reduced food intake compared with similarly treated wild-type mice
- pretreatment with TNFbp attenuates depressive effect of LPS unlike in similarly treated wild-type mice

decreased blood urea nitrogen level
- following ischemic/reperfusion injury, mice exhibit reduced blood urea nitrogen levels at 48 and 72 hours compared with wild-type mice

decreased circulating creatinine level
- following ischemic/reperfusion injury, mice exhibit reduced serum creatinine levels at 48 and 72 hours compared with wild-type mice

decreased susceptibility to kidney reperfusion injury
- following ischemic/reperfusion injury, mice exhibit reduced blood urea nitrogen and creatinine levels at 48 and 72 hours with reduced polymorphonuclear leukocyte infiltration compared with wild-type mice
- Normal - however, tubular damage is normal

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

Genotype: Il1r1^tm1Imx/Il1r1^tm1Imx
B6.129S7-Il1r1/J

adipose tissue phenotype

increased abdominal fat pad weight
- at 19 months, intra-abdominal fat mass is increased 1.5- to 1.7-fold compared with wild-type mice

increased gonadal fat pad weight
- in older mice

increased inguinal fat pad weight
- in older mice

increased mesenteric fat pad weight
- in older mice

increased percent body fat/body weight
- in older mice

increased retroperitoneal fat pad weight
- in older mice

increased total body fat amount
- 2-fold at 9 months of age
- Normal - however, mice exhibit normal body fat at 4 months of age

cardiovascular system phenotype

abnormal vascular wound healing
- following carotid ligation, mice exhibit a 19-fold reduction in neointima/media area, 3.4-fold increase in lumen area, and decrease in total vessel area compared with wild-type mice
- neointima formation following carotid ligation is disrupted to a greater extent when null mice transplanted with null bone marrow compared when null mice are receive wild-type bone marrow or wild-type mice receive null bone marrow

growth/size/body region phenotype

abnormal lean body mass
- older mice exhibit a decrease in percentage lean body mass but an increase in absolute lean body mass compared with wild-type mice

increased body length
- in older mice

increased body mass index
- in older mice

increased body weight
- after 5 to 6 months

increased growth rate
- in older mice

increased susceptibility to age related obesity

weight loss
- following S. aureus infection

homeostasis/metabolism phenotype

abnormal vascular wound healing
- following carotid ligation, mice exhibit a 19-fold reduction in neointima/media area, 3.4-fold increase in lumen area, and decrease in total vessel area compared with wild-type mice
- neointima formation following carotid ligation is disrupted to a greater extent when null mice transplanted with null bone marrow compared when null mice are receive wild-type bone marrow or wild-type mice receive null bone marrow

decreased circulating interleukin-18 level
- 24 hours following S. aureus infection

decreased circulating interleukin-6 level
- 4 and 24 hours following S. aureus infection

decreased transforming growth factor level
- within wound fluids on day 1 of wound healing

enhanced wound healing
- after wound healing, mice exhibit decreased scar width and depth compared with wild-type mice
- deep tissue wounds exhibit 3-fold less fibrosis compared to in wild-type mice
- Normal - however, mice exhibit normal cellular infiltration and tensile strength of skin wounds

impaired glucose tolerance
- following glucose challenge, older mice exhibit impaired plasma glucose elimination compared with wild-type mice

increased circulating insulin level
- 2-fold in 9 and 11 month old mice

increased circulating insulin-like growth factor I level
- in older mice

increased circulating interleukin-1 beta level
- 96 hours following S. aureus infection

increased circulating interleukin-18 level
- 96 hours following S. aureus infection

increased circulating leptin level
- 2-fold in 9 and 11 month old mice

increased respiratory quotient
- during the first half of the dark cycle

insulin resistance
- in older mice

immune system phenotype

decreased circulating interleukin-18 level
- 24 hours following S. aureus infection

decreased circulating interleukin-6 level
- 4 and 24 hours following S. aureus infection

decreased interleukin-6 secretion
- in spleen cells stimulated with formalin-killed S. aureus infection for 48 hours
- within wound fluids on days 1, 3, 5, 10, and 14 of wound healing

decreased tumor necrosis factor secretion
- in spleen cells stimulated with formalin-killed S. aureus infection

increased circulating interleukin-1 beta level
- 96 hours following S. aureus infection

increased circulating interleukin-18 level
- 96 hours following S. aureus infection

increased susceptibility to bacterial infection
- following S. aureus infection, mice exhibit severe septicemia, increased weight loss, increased frequency and severity of arthritis, increased bacterial load, and decreased survival compared with wild-type mice

increased susceptibility to bacterial infection induced morbidity/mortality
- following S. aureus infection

increased susceptibility to induced arthritis
- following S. aureus infection

sepsis
- following S. aureus infection

liver/biliary system phenotype

increased liver weight
- in older mice

mortality/aging

increased susceptibility to bacterial infection induced morbidity/mortality
- following S. aureus infection

nervous system phenotype

abnormal nervous system electrophysiology
- following administration of kainate, Purkinje cells fail to exhibit an increase in firing rate unlike wild-type cells

skeleton phenotype

increased susceptibility to induced arthritis
- following S. aureus infection

behavior/neurological phenotype

abnormal food intake
- preobese mice exhibit mild leptin resistance compared with wild-type mice

decreased anxiety-related response
- mice exhibit increased latency to enter into the dark chamber in a light/dark test compared with wild-type mice
- mice exhibit reduced latency to drink in a novelty-induced hypophagia test compared with wild-type mice
- mice spend more time in the open arms of an elevated plus maze compared with wild-type mice

enhanced contextual conditioning behavior

hypoactivity
- during the dark phase at 4 months

Genotype: Il1r1^tm1Imx/Il1r1^tm1Imx
B6.129S7-Il1r1

mammalian phenotype

immune system phenotype
- Normal - mice co-housed with wild-type mice do not affect the susceptibility to induced colitis of wild-type mice

References

Glaccum MB; Stocking KL; Charrier K; Smith JL; Willis CR; Maliszewski C ; Livingston DJ ; Peschon JJ ; Morrissey PJ. 1997. Phenotypic and functional characterization of mice that lack the type I receptor for IL-1. J Immunol 159(7):3364-71PubMed: 9317135 MGI: J:43088

Additional - Il1r1^tm1Imx related

Technical Support

Contact Technical Support

Genotyping Protocols
- High Resolution Melting: Il1r1^tm1Imx-Alternate 1
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

This strain may be maintained by homozygous sibling matings. Expected coat color from breeding is black.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Homozygote
Appearance
- black
  Related Genotype: a/a
Citation
When using the Il1r1^- mouse strain in a publication, please cite the originating article(s) and include JAX stock #003245 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX11 (Maximum)

Pricing & Availability

Repository Live

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Homozygous for Il1r1<tm1Imx>

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.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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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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Also Known As: Il1r1-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Il1r1tm1Imx

Allele Symbol: Il1r1tm1Imx

Disease Terms

Research Areas By Genotype

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

Genotype: Il1r1tm1Imx related

Mammalian Phenotype Terms by Genotype

Genotype: Il1r1tm1Imx/Il1r1tm1Imxinvolves: 129 * C57BL/6

craniofacial phenotype

skeleton phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

immune system phenotype

Genotype: Il1r1tm1Imx/Il1r1tm1Imxinvolves: 129S7/SvEvBrd

craniofacial phenotype

growth/size/body region phenotype

hematopoietic system phenotype

immune system phenotype

skeleton phenotype

Genotype: Il1r1tm1Imx/Il1r1tm1Imxinvolves: 129S7/SvEvBrd * C57BL/6

growth/size/body region phenotype

immune system phenotype

renal/urinary system phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

Genotype: Il1r1tm1Imx/Il1r1tm1ImxB6.129S7-Il1r1/J

adipose tissue phenotype

cardiovascular system phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

immune system phenotype

liver/biliary system phenotype

mortality/aging

nervous system phenotype

skeleton phenotype

behavior/neurological phenotype

Genotype: Il1r1tm1Imx/Il1r1tm1ImxB6.129S7-Il1r1

mammalian phenotype

References

Additional - Il1r1tm1Imx related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Appearance

Citation

Animal Health Reports

Live Mouse

Cryorecovery - Pricing

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: Il1r1^-

Il1r1^tm1Imx

Allele Symbol: Il1r1^tm1Imx

Genotype: Il1r1^tm1Imx related

Genotype: Il1r1^tm1Imx/Il1r1^tm1Imx
involves: 129 * C57BL/6

Genotype: Il1r1^tm1Imx/Il1r1^tm1Imx
involves: 129S7/SvEvBrd

Genotype: Il1r1^tm1Imx/Il1r1^tm1Imx
involves: 129S7/SvEvBrd * C57BL/6

Genotype: Il1r1^tm1Imx/Il1r1^tm1Imx
B6.129S7-Il1r1/J

Genotype: Il1r1^tm1Imx/Il1r1^tm1Imx
B6.129S7-Il1r1

Additional - Il1r1^tm1Imx related