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.
Miguel J. Stadecker, Tufts Medical School
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.
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.
|Allele Name||targeted mutation 1, Jeanne Magram|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||IL-12 p40-; Il-12/23p40 KO; IL-12-; Il12b-; IL-12btm1 Jm; IL-12KO; IL-12p40-; IL12p40-; IL-12p40-; IL-12p40-KO; p40-|
|Gene Symbol and Name||Il12b, interleukin 12b|
|Strain of Origin||129S1/Sv-Oca2+ Tyr+ Kitl+|
|Molecular Note||A neomycin resistance cassette replaced a portion of exon 3 of the gene.|
|Mutations Made By|| |
Dr. Jeanne Magram, Celsius Therapeutics
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.
When using the CBA.129S1(B6)-Il12btm1Jm/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #019002 in your Materials and Methods section.