Overview

These IL-12p40-deficient CBA mice exhibit less severe hepatic inflammation in response to schistosome infection when compared to wildtype controls, and have applications in studies related to the Th17 cell immune response to parasitic infection.

Donating Investigator

Miguel J. Stadecker, Tufts Medical School

Genetic overview

Genetic Background	Generation

Il12b^tm1Jm

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Il12b	interleukin 12b

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Research Applications

Immunology, Inflammation and Autoimmunity Research
Cancer Research
Research Tools

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Il12b, interleukin 12 beta, encodes the 40 kD cytokine receptor-like subunit of interleukin 12, a cytokine secreted by activated macrophages and important in the development and maintenance of memory/effector Th1 cells in long term immune responses to intracellular pathogens. CBA/J inbred mice are more susceptible to schistosomiasis, developing a more severe perioval granulomatous inflammation when compared to the C57BL/6 inbred strain. These mice carry a targeted mutation of Il12b, interleukin 12 beta, in which part of exon 3 is replaced by a PGK-Neo cassette. No bioactive IL-12 protein is detected by ELISA analysis of schistosome egg- or LPS-stimulated dendritic cells derived from the bone marrow of homozygotes. Schistosome-infected homozygotes exhibit reduced granulomatous inflammation (smaller granuloma size, reduced serum aspartate aminotransferase level) and produce lower levels of IL17 and IFNG when compared to wildtype controls. The Donating Investigator reports that although homozygotes are viable, homozygous females are difficult to breed. During back-crossing, the Y chromosome was not fixed to the CBA/J genetic background.

Development

A targeting vector containing a PGK-Neo cassette was used to disrupt part of exon 3. The construct was electroporated into 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺ derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The mice were back-crossed to to C57BL/6 for 9 generations, and to C57BL/6J for at least one generation. The mice were then back-crossed to CBA/J for 10 generations.
Upon arrival at The Jackson Laboratory, the mice were crossed to CBA/J (Stock No. 000656) at least once to establish the colony.

Control Suggestions

Noncarrier
000656 CBA/J

Additional Information

Considerations for Choosing Controls

Selected References

Shainheit MG; Lasocki KW; Finger E; Larkin BM; Smith PM; Sharpe AH; Dinarello CA; Rutitzky LI; Stadecker MJ. 2011. The pathogenic Th17 cell response to major schistosome egg antigen is sequentially dependent on IL-23 and IL-1beta. J Immunol 187(10):5328-35PubMed: 22003203 MGI: J:179614
Magram J; Connaughton SE; Warrier RR; Carvajal DM; Wu CY; Ferrante J; Stewart C; Sarmiento U; Faherty DA; Gately MK. 1996. IL-12-deficient mice are defective in IFN gamma production and type 1 cytokine responses. Immunity 4(5):471-81PubMed: 8630732 MGI: J:33141

View All References

Genetics

Il12b^tm1Jm

Allele Symbol: Il12b^tm1Jm

Allele Name	targeted mutation 1, Jeanne Magram
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Il12b^tm1Jm; targeted mutation 1, Jeanne Magram
Gene Symbol and Name	Il12b, interleukin 12b
Gene Synonym(s)	CLMF; CLMF2; IL-23 subunit p40; Il12; IL-12 p40; IL-12B; Il-12p40; IMD28; NKSF; NKSF2; Il-12b; IMD29; Il-12b
Strain of Origin	129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Chromosome	11
Molecular Note	A neomycin resistance cassette replaced a portion of exon 3 of the gene.
Mutations Made By	Dr. Jeanne Magram, Boehringer Ingelheim Pharmaceuticals,Inc

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

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

Genotype: Il12b^tm1Jm 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: Il12b^tm1Jm/Il12b^tm1Jm
B6.129S1-Il12b/J

craniofacial phenotype

alveolar process atrophy
- 3 fold increase in alveolar bone loss at 30 weeks relative to mice at 6 and 16 weeks

immune system phenotype

abnormal CD8-positive, alpha-beta T cell physiology
- dramatic increase in the number of cytotoxic CD8+ cells in the dermis and epidermis of carcinogen treated skin

abnormal granulocyte physiology
- fewer than expected granulocytes in the dermis of carcinogen treated skin

abnormal lymphocyte physiology
- lymph node cells from keyhole limpet hemocyanin (KLH) immunized mice are severely impaired in their ability to produce IFNG when cultured with KLH; however, their production of IL4 is increased

abnormal macrophage physiology
- fewer than expected macrophages in the dermis of carcinogen treated skin

abnormal NK cell physiology
- mean NK lytic activity is about 66% of controls; however when cultured with IL2 lytic activity is similar to controls

decreased circulating interferon-gamma level
- serum levels of IFNG in LPS-injected mice are only 17 +/- 5% of LPS-induced controls

decreased interleukin-17 secretion
- barely detectable levels of IL17 in the skin after carcinogen treatment unlike wild-type mice which express high levels of IL17

decreased susceptibility to type IV hypersensitivity reaction
- specific foot pad swelling 48 hours after challenge with methylated bovine serum albumin is inhibited by 47 +/- 3% compared to wild-type mice; however, cytotoxic T lymphocyte responses are similar to wild-type

increased susceptibility to bacterial infection
- vaccination does not produce a protective response to M. tuberculosis

growth/size/body region phenotype

alveolar process atrophy
- 3 fold increase in alveolar bone loss at 30 weeks relative to mice at 6 and 16 weeks

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

neoplasm

decreased incidence of tumors by chemical induction
- however, there is an increase in the incidence of tumors following intradermal challenge with PDV squamous carcinoma cells
- resistant to induction of papillomas compared to wild-type mice after treatment with DMBA and TPA in a 2 step skin carcinogenesis protocol

skeleton phenotype

alveolar process atrophy
- 3 fold increase in alveolar bone loss at 30 weeks relative to mice at 6 and 16 weeks

hematopoietic system phenotype

abnormal CD8-positive, alpha-beta T cell physiology
- dramatic increase in the number of cytotoxic CD8+ cells in the dermis and epidermis of carcinogen treated skin

abnormal granulocyte physiology
- fewer than expected granulocytes in the dermis of carcinogen treated skin

abnormal lymphocyte physiology
- lymph node cells from keyhole limpet hemocyanin (KLH) immunized mice are severely impaired in their ability to produce IFNG when cultured with KLH; however, their production of IL4 is increased

abnormal macrophage physiology
- fewer than expected macrophages in the dermis of carcinogen treated skin

abnormal NK cell physiology
- mean NK lytic activity is about 66% of controls; however when cultured with IL2 lytic activity is similar to controls

homeostasis/metabolism phenotype

decreased circulating interferon-gamma level
- serum levels of IFNG in LPS-injected mice are only 17 +/- 5% of LPS-induced controls

decreased incidence of tumors by chemical induction
- however, there is an increase in the incidence of tumors following intradermal challenge with PDV squamous carcinoma cells
- resistant to induction of papillomas compared to wild-type mice after treatment with DMBA and TPA in a 2 step skin carcinogenesis protocol

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

Genotype: Il12b^tm1Jm/Il12b^tm1Jm
129S1/Sv-Il12b

hematopoietic system phenotype

abnormal CD4-positive, alpha-beta T cell physiology
- 75 days after infection Ifng mRNA expression in CD4+ cells is more than 50-fold lower than in wild-type
- 75 days after infection Il4 mRNA expression in CD4+ cells is 100-fold higher than in wild-type
- draining lymph node cells in L. major infected mice produce significantly more IL4 compared to IFNG in contrast to wild-type mice which express more IFNG than IL4

immune system phenotype

abnormal CD4-positive, alpha-beta T cell physiology
- 75 days after infection Ifng mRNA expression in CD4+ cells is more than 50-fold lower than in wild-type
- 75 days after infection Il4 mRNA expression in CD4+ cells is 100-fold higher than in wild-type
- draining lymph node cells in L. major infected mice produce significantly more IL4 compared to IFNG in contrast to wild-type mice which express more IFNG than IL4

decreased susceptibility to type IV hypersensitivity reaction
- do not show any delayed type hypersensitivity response to application of Leishmania antigen to the uninfected footpad 41 days after initial infection with L. major

increased susceptibility to parasitic infection
- 75 days after infection with L. major parasite numbers in the draining lymph nodes are increased 400-fold compared to wild-type mice
- develop large lesions unlike wild-type 129S1/Sv mice after infection with Leishmania major

Genotype: Il12b^tm1Jm/Il12b^tm1Jm
involves: 129S1/SvImJ

hematopoietic system phenotype

abnormal T-helper 1 physiology
- in vivo Th1 cell response is impaired as indicated by the low amounts of IFN-gamma produced by T cells in response to M. bovis antigens

impaired natural killer cell mediated cytotoxicity
- normal level of target cell killing can be restored by in vivo pretreatment with IL-18 for two days or the addition of IL-18 to the co-culture
- the killing activity of splenic NK cells is about 2/3^rds that of wild-type mice as measured by in vitro co-culturing with YAC-1 target cells

immune system phenotype

abnormal T-helper 1 physiology
- in vivo Th1 cell response is impaired as indicated by the low amounts of IFN-gamma produced by T cells in response to M. bovis antigens

decreased interferon-gamma secretion
- splenic T cells produce about 1/4^th the amount of IFN-gamma as T cells from wild-type mice 14 days after injection with heat killed M. Bovis

impaired natural killer cell mediated cytotoxicity
- normal level of target cell killing can be restored by in vivo pretreatment with IL-18 for two days or the addition of IL-18 to the co-culture
- the killing activity of splenic NK cells is about 2/3^rds that of wild-type mice as measured by in vitro co-culturing with YAC-1 target cells

Genotype: Il12b^tm1Jm/Il12b^tm1Jm
involves: 129S1/Sv

immune system phenotype

increased susceptibility to bacterial infection induced morbidity/mortality
- mice died before day 12 after inoculation with C. rodentium

mortality/aging

increased susceptibility to bacterial infection induced morbidity/mortality
- mice died before day 12 after inoculation with C. rodentium

References

Shainheit MG; Lasocki KW; Finger E; Larkin BM; Smith PM; Sharpe AH; Dinarello CA; Rutitzky LI; Stadecker MJ. 2011. The pathogenic Th17 cell response to major schistosome egg antigen is sequentially dependent on IL-23 and IL-1beta. J Immunol 187(10):5328-35PubMed: 22003203 MGI: J:179614
Magram J; Connaughton SE; Warrier RR; Carvajal DM; Wu CY; Ferrante J; Stewart C; Sarmiento U; Faherty DA; Gately MK. 1996. IL-12-deficient mice are defective in IFN gamma production and type 1 cytokine responses. Immunity 4(5):471-81PubMed: 8630732 MGI: J:33141

Additional - Il12b^tm1Jm related

Technical Support

Contact Technical Support

Genotyping Protocols
- Separated PCR:Il12b^tm1Jm
- Separated PCR:Il12b^tm1Jm
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred by crossing heterozygous females with homozygous males. The Donating Investigator reports that although homozygotes are viable, homozygous females are difficult to breed.
- Additional Breeding and Husbandry Support
Citation
When using the CBA.129S1(B6)-Il12b^tm1Jm/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #019002 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	Genotype	Price
	Heterozygous for Il12b<tm1Jm>

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	CBA.129S1(B6)-Il12b<tm1Jm>/J	$2595.00
Frozen Mouse Embryo	CBA.129S1(B6)-Il12b<tm1Jm>/J	$2595.00
Frozen Mouse Embryo	CBA.129S1(B6)-Il12b<tm1Jm>/J	$3373.50
Frozen Mouse Embryo	CBA.129S1(B6)-Il12b<tm1Jm>/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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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Il12btm1Jm

Allele Symbol: Il12btm1Jm

Disease Terms

Research Areas By Genotype

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

Genotype: Il12btm1Jm related

Mammalian Phenotype Terms by Genotype

Genotype: Il12btm1Jm/Il12btm1JmB6.129S1-Il12b/J

craniofacial phenotype

immune system phenotype

growth/size/body region phenotype

mortality/aging

neoplasm

skeleton phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

Genotype: Il12btm1Jm/Il12btm1Jm129S1/Sv-Il12b

hematopoietic system phenotype

immune system phenotype

Genotype: Il12btm1Jm/Il12btm1Jminvolves: 129S1/SvImJ

hematopoietic system phenotype

immune system phenotype

Genotype: Il12btm1Jm/Il12btm1Jminvolves: 129S1/Sv

immune system phenotype

mortality/aging

References

Additional - Il12btm1Jm 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

Il12b^tm1Jm

Allele Symbol: Il12b^tm1Jm

Genotype: Il12b^tm1Jm related

Genotype: Il12b^tm1Jm/Il12b^tm1Jm
B6.129S1-Il12b/J

Genotype: Il12b^tm1Jm/Il12b^tm1Jm
129S1/Sv-Il12b

Genotype: Il12b^tm1Jm/Il12b^tm1Jm
involves: 129S1/SvImJ

Genotype: Il12b^tm1Jm/Il12b^tm1Jm
involves: 129S1/Sv

Additional - Il12b^tm1Jm related