Mice that are homozygous for the knock-out mutation are susceptible to Leishmania major infection. 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, do not display any gross physical or behavioral abnormalities and are fertile but poor breeders. No gene product, protein or mRNA, is detected. Lymphocyte development, T cell to B cell ratio and CD4 to CD8 ratio are normal. Naive Th cells activated in vitro preferentially differentiate into Th2 cells. Mutant mice are susceptible to infection when challenged with the intracellular pathogen, Leishmania major. Primary murine embryonic fibroblasts prepared from mutant embryos are partially protected from UV-induced apoptosis. This mutant mouse strain represents a model that may be useful in studies related to signal transduction.
A targeting vector containing a hygromycin phosphotransferase gene driven by the mouse phosphoglycerate kinase promoter and a herpes simplex virus thymidine kinase gene was used to disrupt 5.5kb of genomic sequence, encoding four exons of the targeted gene. The construct was electroporated into 129S1 derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were backcrossed to C57BL/6 mice.
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 may have been on a mixed C57BL/6J x C57BL/6N genetic background.
|Allele Name||targeted mutation 1, Richard Flavell|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Jnk1 -; Jnk1 KO|
|Gene Symbol and Name||Mapk8, mitogen-activated protein kinase 8|
|Strain of Origin||129S1/Sv-Oca2+ Tyr+ Kitl+|
|Molecular Note||A hygromycin resistance cassette replaced a 5.5 kb genomic fragment containing four exons of the gene. Western blot analysis on extracts derived from embryonic fibroblasts of homozygous mice confirmed that no detectable protein was expressed from this allele.|
|Mutations Made By|| |
Dr. Richard Flavell, Yale University School of Medicine
This strain originated on a B6;129S1 background and has been backcrossed for 5 generations on the C57BL/6 background. This strain is maintained by heterozygous crosses, due to poor breeding performance of homozygous mice. Coat color expected from breeding:Black
When using the Jnk1 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004319 in your Materials and Methods section.