Overview

Also Known As: Irf1 KO

Type I interferon gene induction is abnormal in homozygous mice. They exhibit impairment of CD8⁺ T cell and NK cell maturation, impaired IL-12 macrophage production, exclusive Th2 differentiation, and defective Th1.

Donating Investigator

Dr. Ronald Schwartz, National Institutes of Health

Genetic overview

Genetic Background	Generation
	N11F50 (2019-06-14 00:00:00)

Irf1^tm1Mak

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Irf1	interferon regulatory factor 1

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Research Applications

Immunology, Inflammation and Autoimmunity 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 homozygous for the Irf1^tm1Mak targeted mutation are viable and fertile with no major abnormalities. Type I interferon gene induction is abnormal. These mice exhibit impairment of CD8⁺ T cell and NK cell maturation, impaired IL-12 macrophage production, exclusive Th2 differentiation, and defective Th1. While these mice are highly susceptible to infections, they have been reported to be resistant to several autoimmune diseases such as collagen-induced arthritis, experimental autoimmune encephalomyelitis, Helicobacter pylori-induced gastritis, induced lymphocytic thyroiditis, insulitis, or diabetes.

Development

A neomycin resistance cassette replaced a 1.2 kb region of the gene, which encodes for amino acids 63 - 223, deleting part of the DNA-binding domain of the protein. The construct was electroporated into D3 ES cells and correctly targeted cells were injected into C57BL/6J blastocysts.

Control Suggestions

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Matsuyama T; Kimura T; Kitagawa M; Pfeffer K; Kawakami T; Watanabe N; Kundig TM; Amakawa R; Kishihara K; Wakeham A; et al. 1993. Targeted disruption of IRF-1 or IRF-2 results in abnormal type I IFN gene induction and aberrant lymphocyte development. Cell 75(1):83-97PubMed: 8402903 MGI: J:64286

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Genetics

Irf1^tm1Mak

Allele Symbol: Irf1^tm1Mak

Allele Name	targeted mutation 1, Tak Mak
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Irf1^tm1Mak; targeted mutation 1, Tak Mak
Gene Symbol and Name	Irf1, interferon regulatory factor 1
Gene Synonym(s)	Irf-1; AU020929; IRF-1; expressed sequence AU020929; MAR; Irf-1
Strain of Origin	129S2/SvPas
Chromosome	11
Molecular Note	A neomycin resistance cassette replaced a 1.2 kb region of the gene, which encodes for amino acids 63 - 223, deleting part of the DNA-binding domain of the protein.
Mutations Made By	Dr. Tak Mak, University Health Network/Un of Toronto

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Genotype: Irf1^tm1Mak related

Immunology, Inflammation and Autoimmunity Research
- T Cell Receptor Signaling Defects

Mammalian Phenotype Terms by Genotype

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

Genotype: Irf1^tm1Mak/Irf1^tm1Mak
either: (involves: 129S2/SvPas * C57BL/6J) or (involves: 129S2/SvPas * C57BL/6J * DBA/2)

hematopoietic system phenotype

abnormal T cell number
- CD8+/CD4+ T cell ratio is lower than wild-type or Irf2-deficient mice during course of LCMV infection

decreased CD8-positive, alpha-beta T cell number
- 10-fold reduction in TCR alpha-beta CD4-CD8+ T cells is observed in peripheral blood, spleen, thymus, and lymph nodes

increased CD4-positive, alpha beta T cell number
- CD4+CD8- T cells are often but not always increased in number in homozygotes

increased double-positive T cell number
- numbers are normal or slightly increased in thymi

mammalian phenotype

immune system phenotype
- Normal - humoral response to vesicular stomatitis virus challenge is normal; kinetics of immunoglobulin class switching and antibody levels are comparable to wild-type mice

immune system phenotype

abnormal response to infection
- significantly reduced cytotoxic responses against LCMV-infected target cells are observed

abnormal T cell number
- CD8+/CD4+ T cell ratio is lower than wild-type or Irf2-deficient mice during course of LCMV infection

decreased CD8-positive, alpha-beta T cell number
- 10-fold reduction in TCR alpha-beta CD4-CD8+ T cells is observed in peripheral blood, spleen, thymus, and lymph nodes

increased CD4-positive, alpha beta T cell number
- CD4+CD8- T cells are often but not always increased in number in homozygotes

increased double-positive T cell number
- numbers are normal or slightly increased in thymi

Genotype: Irf1^tm1Mak/Irf1⁺
either: (involves: 129S2/SvPas * C57BL/6J) or (involves: 129S2/SvPas * C57BL/6J * DBA/2)

normal phenotype

no abnormal phenotype detected
- Normal - mice are viable and fertile, with no detectable abnormalities

Genotype: Irf1^tm1Mak/Irf1^tm1Mak
involves: 129S2/SvPas

cellular phenotype

abnormal DNA repair
- cultured hepatocytes from 6-10 week males show a defect in DNA repair in an assay in which repair of a UV-damaged reporter plasmid by wild-type and null hepatocytes; recovery of reporter activity by Irf1-deficient hepatocytes is significantly lower than that of wild-type or Trp53-deficient cells
- hat of wild-type or Trp53-deficient cells

homeostasis/metabolism phenotype

abnormal DNA repair
- cultured hepatocytes from 6-10 week males show a defect in DNA repair in an assay in which repair of a UV-damaged reporter plasmid by wild-type and null hepatocytes; recovery of reporter activity by Irf1-deficient hepatocytes is significantly lower than that of wild-type or Trp53-deficient cells
- hat of wild-type or Trp53-deficient cells

mammalian phenotype

cellular phenotype
- Normal - 6-12 hours after UV irradiation, hepatocytes arrest in at G₁/S, similar to wild-type cells
- Normal - apoptosis following UV-induced damage is similar in mutant primary hepatocytes from 6-10 week males and wild-type cells

Genotype: Irf1^tm1Mak/Irf1^tm1Mak
involves: 129S2/SvPas * C57BL/6J

cardiovascular system phenotype

abnormal vascular wound healing
- 28 days after induction of flow cessation in the common carotid artery, a significant increase of neointima formation was observed proximal of the ligation suture in mutants compared to control wild-type mice

homeostasis/metabolism phenotype

abnormal vascular wound healing
- 28 days after induction of flow cessation in the common carotid artery, a significant increase of neointima formation was observed proximal of the ligation suture in mutants compared to control wild-type mice

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

Genotype: Irf1^tm1Mak/Irf1^tm1Mak
B6.129S2-Irf1/J

hematopoietic system phenotype

abnormal lymphocyte physiology
- IL12 treatment can rescue the impairment in IFNG production
- impairment in the ability to produce IFNG in response to Con A stimulation

mortality/aging

increased sensitivity to xenobiotic induced morbidity/mortality
- increase in mortality following a single dose of N-methyl-N-nitrosourea (MNU) compared to similarly treated wild-type controls
- treatment with recombinant IL12 significantly improves survival of MNU treated mice

neoplasm

increased incidence of tumors by chemical induction
- following a single dose of MNU most mice develop massive lymphoid neoplasias
- treatment with recombinant IL12 reduces the incidence of lymphomas in MNU treated mice

increased lymphoma incidence
- following a single dose of MNU compared to similarly treated wild-type controls

homeostasis/metabolism phenotype

abnormal circulating alanine transaminase level
- when subjected to warm ischemia/reperfusion (I/R), 60 minutes of warm hepatic ischemia followed by 6 hours of reperfusion significantly increase serum ALT levels in controls, but levels in treated mutants are ~60% lower than I/R-treated wild-type mice

increased incidence of tumors by chemical induction
- following a single dose of MNU most mice develop massive lymphoid neoplasias
- treatment with recombinant IL12 reduces the incidence of lymphomas in MNU treated mice

increased sensitivity to xenobiotic induced morbidity/mortality
- increase in mortality following a single dose of N-methyl-N-nitrosourea (MNU) compared to similarly treated wild-type controls
- treatment with recombinant IL12 significantly improves survival of MNU treated mice

immune system phenotype

abnormal lymphocyte physiology
- IL12 treatment can rescue the impairment in IFNG production
- impairment in the ability to produce IFNG in response to Con A stimulation

decreased interferon-gamma secretion
- by lymphocytes following Con A stimulation
- IL12 treatment can rescue the impairment in IFNG production

References

Matsuyama T; Kimura T; Kitagawa M; Pfeffer K; Kawakami T; Watanabe N; Kundig TM; Amakawa R; Kishihara K; Wakeham A; et al. 1993. Targeted disruption of IRF-1 or IRF-2 results in abnormal type I IFN gene induction and aberrant lymphocyte development. Cell 75(1):83-97PubMed: 8402903 MGI: J:64286

Additional References

Kimura T; Nakayama K; Penninger J; Kitagawa M; Harada H; Matsuyama T; Tanaka N; Kamijo R; Vilcek J; Mak TW; Taniguchi T. 1994. Involvement of the IRF-1 transcription factor in antiviral responses to interferons. Science 264(5167):1921-4PubMed: 8009222 MGI: J:18880
Liu J; Cao S; Herman LM; Ma X. 2003. Differential regulation of interleukin (IL)-12 p35 and p40 gene expression and interferon (IFN)-gamma-primed IL-12 production by IFN regulatory factor 1. J Exp Med 198(8):1265-76PubMed: 14568984 MGI: J:86244
Hancock WW; Szaba FM; Berggren KN; Parent MA; Mullarky IK; Pearl J; Cooper AM; Ely KH; Woodland DL; Kim IJ; Blackman MA; Johnson LL; Smiley ST. 2004. Intact type 1 immunity and immune-associated coagulative responses in mice lacking IFN gamma-inducible fibrinogen-like protein 2. Proc Natl Acad Sci U S A 101(9):3005-10PubMed: 14976252 MGI: J:88648

Additional - Irf1^tm1Mak related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR:Irf1^tm1Mak
- Standard PCR:Irf1^tm1Mak
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

When maintaining the live colony, homozygous mice may be bred together. The 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 Irf1 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #002762 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX11 (Maximum)

Pricing & Availability

Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous for Irf1<tm1Mak>

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	B6.129S2-Irf1<tm1Mak>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6.129S2-Irf1<tm1Mak>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6.129S2-Irf1<tm1Mak>/J Frozen Embryos	$3373.50
Frozen Mouse Embryo	B6.129S2-Irf1<tm1Mak>/J Frozen Embryos	$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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General Terms and Conditions

Questions about Terms of Use

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Licensing Information

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Also Known As: Irf1 KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Irf1tm1Mak

Allele Symbol: Irf1tm1Mak

Disease Terms

Research Areas By Genotype

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

Genotype: Irf1tm1Mak related

Mammalian Phenotype Terms by Genotype

Genotype: Irf1tm1Mak/Irf1tm1Makeither: (involves: 129S2/SvPas * C57BL/6J) or (involves: 129S2/SvPas * C57BL/6J * DBA/2)

hematopoietic system phenotype

mammalian phenotype

immune system phenotype

Genotype: Irf1tm1Mak/Irf1+either: (involves: 129S2/SvPas * C57BL/6J) or (involves: 129S2/SvPas * C57BL/6J * DBA/2)

normal phenotype

Genotype: Irf1tm1Mak/Irf1tm1Makinvolves: 129S2/SvPas

cellular phenotype

homeostasis/metabolism phenotype

mammalian phenotype

Genotype: Irf1tm1Mak/Irf1tm1Makinvolves: 129S2/SvPas * C57BL/6J

cardiovascular system phenotype

homeostasis/metabolism phenotype

Genotype: Irf1tm1Mak/Irf1tm1MakB6.129S2-Irf1/J

hematopoietic system phenotype

mortality/aging

neoplasm

homeostasis/metabolism phenotype

immune system phenotype

References

Additional References

Additional - Irf1tm1Mak related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Appearance

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

Irf1^tm1Mak

Allele Symbol: Irf1^tm1Mak

Genotype: Irf1^tm1Mak related

Genotype: Irf1^tm1Mak/Irf1^tm1Mak
either: (involves: 129S2/SvPas * C57BL/6J) or (involves: 129S2/SvPas * C57BL/6J * DBA/2)

Genotype: Irf1^tm1Mak/Irf1⁺
either: (involves: 129S2/SvPas * C57BL/6J) or (involves: 129S2/SvPas * C57BL/6J * DBA/2)

Genotype: Irf1^tm1Mak/Irf1^tm1Mak
involves: 129S2/SvPas

Genotype: Irf1^tm1Mak/Irf1^tm1Mak
involves: 129S2/SvPas * C57BL/6J

Genotype: Irf1^tm1Mak/Irf1^tm1Mak
B6.129S2-Irf1/J

Additional - Irf1^tm1Mak related