Overview

Also Known As: ICE^-, Casp1-

This strain, relevant to studies of inflammation and cell death, carries a knockout allele of the Casp1 gene as well as an incidental Casp4 deficiency.

Donating Investigator

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

Genetic overview

Genetic Background	Generation
	N10pN1+F17 (2019-06-13 00:00:00)

Casp1^tm1Flv

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Casp1	caspase 1

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Research Applications

Apoptosis Research
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

Caspase 1 (also known as interleukin-1beta converting enzyme or ICE) knockout mice lack part of exons 6 and 7 of the Casp1 gene and do not process pro-IL-1beta (IL1B) or pro-IL-18 (IL18) into their mature forms. Therefore, stimulation of CASP1-deficient monocytes by activators of multiple pattern recognition receptors that form inflammasomes with CASP1 (including Nlrp3 and Nlrc4) fail to secrete mature IL1B or IL18. In addition, secretion of IL-1alpha (IL1A) is reduced. Caspase-1 is involved in particular cell death pathways including pyroptosis, and caspase-1 deficient cells demonstrate reduced lysis upon infection with certain pathogens.

It has recently been confirmed that these mice are de facto Casp1/Casp4(formerly called caspase 11) double knockout mice. This is resultant from the dysfunctional nature of the naturally occuring 129 Casp4 allele. These Casp1 knockout mice were produced in embryonic stem (ES) cells on a 129S2 background.

Homozygous Casp1 targeted mutant mice are viable, fertile, and show no gross abnormalities in appearance, body weight or organ size for at least the first 16 weeks of life. Homozygotes are born at predicted Mendelian frequencies and the absence of mRNA was confirmed by RT-PCR analysis.

Development

A 2.5 kb EcoRI-HindIII fragment containing caspase 1 exons 4-6 and a 1.3 kb EcoRI-SmaI fragment containing exons 8-10 were subcloned with the neomycin resistance gene cassette in a thymidine kinase gene-expressing plasmid to generate the targeting vector. The vector was linearized and introduced into 129S2/SvPas-derived embryonic stem (ES) cells by electroporation. 63 clones resistant to G418 and Gancyclovir were screened by PCR using and exon 10 primer and a neo cassette specific primer. One correctly targeted clone was confirmed by Southern blot analysis. Chimeric mice were generated from the targeted ES cells and chimeras bred to germline. The donating investigator reported that the progeny were backcrossed at least 10 generation on C57BL/6N background (see SNP note below).

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 rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 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

005304 C57BL/6NJ

Additional Information

Considerations for Choosing Controls

Selected References

Kuida K; Lippke JA; Ku G; Harding MW; Livingston DJ; Su MS; Flavell RA. 1995. Altered cytokine export and apoptosis in mice deficient in interleukin-1 beta converting enzyme. Science 267(5206):2000-3PubMed: 7535475 MGI: J:24258

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Genetics

Casp1^tm1Flv

Allele Symbol: Casp1^tm1Flv

Allele Name	targeted mutation 1, Richard Flavell
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	targeted mutation 1, Richard Flavell; Casp1^tm1Flv
Gene Symbol and Name	Casp1, caspase 1
Gene Synonym(s)	Caspase-1; IL1BC; interleukin 1 beta-converting enzyme; P45; Il1bc; ICE; interleukin 1 beta convertase; Il1bc; Ice
Strain of Origin	129S2/SvPas
Chromosome	9
General Note	The ES cells used to generate this allele contain the linked Casp4^del truncated allele that fails to produce a functional Casp4. Phenotypes associated with this allele may be affected by the presence of the Casp^del allele. J:193522
Molecular Note	A genomic fragment containing part of exon 6 and exon 7 was replaced with a neomycin selection cassette. RT-PCR analysis on samples derived from homozygous mice demonstrated that no detectable transcript was produced from this allele.
Mutations Made By	Dr. Richard Flavell, Yale University School of Medicine

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Apoptosis Research
Immunology, Inflammation and Autoimmunity Research
- Inflammation
- 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: Casp1^tm1Flv/Casp1^tm1Flv Casp4^del/Casp4^del
involves: 129S2/SvPas * C57BL/6

cellular phenotype

decreased thymocyte apoptosis
- Fas mediated apoptosis in thymocytes is suppressed

impaired neutrophil chemotaxis
- following stimulation with monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD), neutrophil recruitment is impaired

renal tubular necrosis
- reduced after ischemic reperfusion as compared to controls

renal/urinary system phenotype

kidney failure
- ischemic acute renal failure is less severe than in controls

renal tubular necrosis
- reduced after ischemic reperfusion as compared to controls

endocrine/exocrine gland phenotype

decreased thymocyte apoptosis
- Fas mediated apoptosis in thymocytes is suppressed

hematopoietic system phenotype

decreased thymocyte apoptosis
- Fas mediated apoptosis in thymocytes is suppressed

impaired neutrophil chemotaxis
- following stimulation with monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD), neutrophil recruitment is impaired

homeostasis/metabolism phenotype

decreased circulating interferon-gamma level
- serum levels are reduced in mice given Il12 daily

immune system phenotype

abnormal cytokine secretion

decreased circulating interferon-gamma level
- serum levels are reduced in mice given Il12 daily

decreased interferon-gamma secretion
- significantly reduced levels of Ifn gamma are induced by Il12 in splenocytes

decreased interleukin-1 alpha secretion
- no Il1 alpha is released by monocytes in response to LPS

decreased interleukin-1 beta secretion
- no Il1 beta is released by monocytes in response to LPS

decreased interleukin-18 secretion
- Il12 treatment fails to cause increased Il18 release but liver and spleen levels increase comparable to controls
- significantly lower levels of Il18 are released by cultured splenocytes

decreased interleukin-6 secretion
- secretion by monocytes in response to LPS is reduced

decreased susceptibility to endotoxin shock
- 10 fold increase in survival (from 6% in wild-type to 60%) of mice challenged with a high dose of LPS

decreased susceptibility to experimental autoimmune encephalomyelitis

decreased thymocyte apoptosis
- Fas mediated apoptosis in thymocytes is suppressed

decreased tumor necrosis factor secretion
- secretion by monocytes in response to LPS is reduced

impaired neutrophil chemotaxis
- following stimulation with monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD), neutrophil recruitment is impaired

increased susceptibility to bacterial infection
- macrophages infected with Legionella and cultured for 72 hours show a 200-fold increase in bacterial number

Genotype: Casp1^tm1Flv/Casp1^tm1Flv Casp4^del/Casp4^del
involves: 129S2/SvPas

mortality/aging

decreased sensitivity to induced morbidity/mortality
- only 3 of 16 mice injected with B16M cells die after 12 days compared to all similarly treated wild-type mice

neoplasm

decreased metastatic potential
- mice injected with B16 cells exhibit decreased metastasis volume, an indicator of metastatic growth, compared with similarly treated wild-type mice
- mice injected with B16 cells exhibit reduced metastasis (by volume and density) in the liver compared with similarly treated wild-type mice

decreased tumor growth/size
- mice injected with B16 cells exhibit decreased metastasis volume, an indicator of metastatic growth, compared with similarly treated wild-type mice

Genotype: Casp1^tm1Flv/Casp1^tm1Flv Casp4^del/Casp4^del
involves: 129S2/SvPas * C57BL/6J

homeostasis/metabolism phenotype

decreased incidence of tumors by chemical induction
- mice treated with 7,12-Dimethylbenz(a)anthracene/12-O-Tetradecanoylphorbol-13-acetate (DMBA) exhibit later onset and a lower incidence of tumors compared with type mice

mammalian phenotype

integument phenotype
- Normal - untreated or TPA, TNF or EGF-treated keratinocytes exhibit normal proliferation

neoplasm

decreased incidence of tumors by chemical induction
- mice treated with 7,12-Dimethylbenz(a)anthracene/12-O-Tetradecanoylphorbol-13-acetate (DMBA) exhibit later onset and a lower incidence of tumors compared with type mice

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

Genotype: Casp1^tm1Flv/Casp1^tm1Flv Casp4^del/Casp4^del
B6.129S2-Casp1

cellular phenotype

renal tubular necrosis
- reduced compared to controls after LPS induced acute kidney failure but not significantly

digestive/alimentary phenotype

abnormal gut flora balance
- mice and co-housed wild-type mice exhibit expanded bacterial phylotypes compared with wild-type mice

increased susceptibility to induced colitis
- mice exhibit increased susceptibility to dextran sodium sulfate (DSS)-induced colitis compared with similarly treated wild-type mice
- mice transmit increased susceptibility to DSS-induced colitis to co-housed wild-type mice

immune system phenotype

decreased interleukin-1 beta secretion
- in LPS-primed bone marrow derived macrophages stimulated by S. typhimurium

increased susceptibility to induced colitis
- mice exhibit increased susceptibility to dextran sodium sulfate (DSS)-induced colitis compared with similarly treated wild-type mice
- mice transmit increased susceptibility to DSS-induced colitis to co-housed wild-type mice

renal/urinary system phenotype

decreased renal glomerular filtration rate
- reduced after LPS induced acute kidney failure but less than in controls

kidney failure
- LPS induced acute kidney failure is also less severe

renal tubular necrosis
- reduced compared to controls after LPS induced acute kidney failure but not significantly

References

Kuida K; Lippke JA; Ku G; Harding MW; Livingston DJ; Su MS; Flavell RA. 1995. Altered cytokine export and apoptosis in mice deficient in interleukin-1 beta converting enzyme. Science 267(5206):2000-3PubMed: 7535475 MGI: J:24258

Additional - Casp1^tm1Flv related

Technical Support

Contact Technical Support

Genotyping Protocols
- Separated PCR:Casp1^tm1Flv
- Probe:Casp1^tm1Flv Probe
- Genotyping resources and troubleshooting
Breeding Considerations

When live colonies are maintained, homozygotes or heterozygotes may be bred.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Homozygote
Citation
When using the ICE^- mouse strain in a publication, please cite the originating article(s) and include JAX stock #016621 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX12 (Maximum)

Pricing & Availability

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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous for Casp1<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.129S2-Casp1<tm1Flv>/J	$2595.00
Frozen Mouse Embryo	B6N.129S2-Casp1<tm1Flv>/J	$2595.00
Frozen Mouse Embryo	B6N.129S2-Casp1<tm1Flv>/J	$3373.50
Frozen Mouse Embryo	B6N.129S2-Casp1<tm1Flv>/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.

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Questions about Terms of Use

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Licensing Information

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Also Known As: ICE-, Casp1-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Casp1tm1Flv

Allele Symbol: Casp1tm1Flv

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Casp1tm1Flv/Casp1tm1Flv Casp4del/Casp4delinvolves: 129S2/SvPas * C57BL/6

cellular phenotype

renal/urinary system phenotype

endocrine/exocrine gland phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

Genotype: Casp1tm1Flv/Casp1tm1Flv Casp4del/Casp4delinvolves: 129S2/SvPas

mortality/aging

neoplasm

Genotype: Casp1tm1Flv/Casp1tm1Flv Casp4del/Casp4delinvolves: 129S2/SvPas * C57BL/6J

homeostasis/metabolism phenotype

mammalian phenotype

neoplasm

Genotype: Casp1tm1Flv/Casp1tm1Flv Casp4del/Casp4delB6.129S2-Casp1

cellular phenotype

digestive/alimentary phenotype

immune system phenotype

renal/urinary system phenotype

References

Additional - Casp1tm1Flv related

Genotyping Protocols

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: ICE^-, Casp1-

Casp1^tm1Flv

Allele Symbol: Casp1^tm1Flv

Genotype: Casp1^tm1Flv/Casp1^tm1Flv Casp4^del/Casp4^del
involves: 129S2/SvPas * C57BL/6

Genotype: Casp1^tm1Flv/Casp1^tm1Flv Casp4^del/Casp4^del
involves: 129S2/SvPas

Genotype: Casp1^tm1Flv/Casp1^tm1Flv Casp4^del/Casp4^del
involves: 129S2/SvPas * C57BL/6J

Genotype: Casp1^tm1Flv/Casp1^tm1Flv Casp4^del/Casp4^del
B6.129S2-Casp1

Additional - Casp1^tm1Flv related