In this strain, codon 108 in exon 6 of the endogenous mitogen-activated protein kinase 9 (Mapk9 or c-Jun N-terminal kinase 2 (Jnk2)) gene was mutated from a Methionine (ATG) to a Glycine (GGG). These mice may be useful for studying MAP kinase signaling pathways, JNK activation and regulation, and cellular growth.
Roger J Davis, University of Massachusetts Medical Sch.
In this strain, codon 108 in exon 6 of the endogenous mitogen-activated protein kinase 9 (Mapk9 or c-Jun N-terminal kinase 2 (Jnk2)) gene was mutated from a Methionine (ATG) to a Glycine (GGG). Homozygous mice are viable, fertile, and normal in size. Jnk2 exhibits widespread expression and is involved in the regulation of cellular proliferation, transformation, and apoptosis, and has been implicated in some neurodegenerative diseases, diabetes, and arthritis. Phosphorylation of JNK2 by other MAPK kinases is required for activation. This mutation in JNK2MG/MG mice expands the size of the ATP pocket of JNK2, increasing sensitivity to inactive small molecule inhibition by PP1, allowing for specific reversible JNK2 inhibition. These mice exhibit a loss of JNK2 signaling while maintaining expression, and show an increase in cellular proliferation, motility, and survival. These mice may be useful for studying MAP kinase signaling pathways, JNK activation and regulation, and cellular growth.
A targeting construct was made containing exons 6-7 of the mitogen-activated protein kinase 9 (Mapk9 or Jnk2) gene. Codon 108 in exon 6 was mutated from a Methionine (ATG) to a Glycine (GGG), and a loxP-flanked neomycin (neo) resistance cassette was placed downstream of exon 6. The construct was electroporated into 129S6/SvEvTac-derived TC1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting chimeric mice were bred. These mice were then bred to mice carrying a Prm1-cre transgene (founder line PC3) on a C57BL/6J x 129/Sv background to remove the floxed selection cassette. These Jnk2MG mice were backcrossed for at least 10 generations to C57BL/6J. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1.1, Roger J Davis|
|Allele Type||Targeted (Not Specified)|
|Allele Synonym(s)||Jnk2M108G; Jnk2MG|
|Gene Symbol and Name||Mapk9, mitogen-activated protein kinase 9|
|Promoter||Mapk9, mitogen-activated protein kinase 9, mouse, laboratory|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||Codon 108 was changed from a methionine to a glycine (M108G) in exon 6. A floxed neo was removed via cre mediated recombination.|
|Mutations Made By|| |
Roger Davis, University of Massachusetts Medical Sch.
When maintaining a live colony, homozygous mice may be bred together.
When using the B6.129-Mapk9tm1.1Rjd/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #013538 in your Materials and Methods section.