Th1 cell differentiation is impaired in these mice. Primary murine embryonic fibroblasts prepared from mutant embryos have decreased viability and increased genomic DNA fragmentation with UV irradiation. This mutant mouse strain represents a model that may be useful in studies related to signal transduction.
Dr. Richard A. Flavell, Yale University School of Medicine
Mice that are homozygous for the targeted mutation are viable, normal in size and do not display any gross physical or behavioral abnormalities. No gene product, mRNA or protein, is detected. Mutant mice have normal T cell and B cell development, ratio of CD4+ and CD8+ T cells in the spleen, and numbers of peripheral B cells. Although differentiation of precursor CD4+ T cells into effector Th2 cells is normal, Th1 cell differentiation is impaired. Treatment with IFN-gamma and IL-12 during precursor CD4+ T cell differentiation results in normal Th1 cell development. Primary murine embryonic fibroblasts prepared from mutant embryos have decreased viability and increased genomic DNA fragmentation with UV irradiation. This mutant mouse strain represents a model that may be useful in studies related to signal transduction.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt three exons encoding the protein subdomains VIII and IX (amino acids residues 151-229). The construct was electroporated into 129S2/SvPas derived D3M embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The donating investigator reports that the resulting chimeric animals were backcrossed to C57BL/6 mice (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. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, at least 4 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.
|Allele Name||targeted mutation 1, Richard Flavell|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Jnk2-; Jnk2 KO|
|Gene Symbol and Name||Mapk9, mitogen-activated protein kinase 9|
|Strain of Origin||129S2/SvPas|
|Molecular Note||A neomycin selection cassette replaced a genomic fragment containing three coding exons containing sequences required for protein kinase activity. RT-PCR analysis on RNA derived from thymus of homozygous mice confirmed that no detectable transcript is produced from this allele. Western blot analysis on brain, thymocyte and T cells derived from homozygous mice confirmed that no protein was expressed from this allele.|
|Mutations Made By|| |
Dr. Richard Flavell, Yale University School of Medicine
This strain originated on a B6;129S2 background, has been backcrossed for 5 generations on the C57BL/6 background and is maintained as a homozygote. Coat color expected from breeding:Black
When using the JNK2 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004321 in your Materials and Methods section.