In this knockout strain, a neomycin resistance cassette replaces exon 3 of the endogenous mitogen-activated protein kinase 8 interacting protein 1 (Mapk8ip1 or Jip1) gene. These mice may be useful for studying MAP kinase signaling pathways and stress-induced activation of JNK.
Roger J Davis, University of Massachusetts Medical Sch.
In this strain, a neomycin resistance cassette replaces exon 3 of the endogenous mitogen-activated protein kinase 8 interacting protein 1 (Mapk8ip1 or Jip1) gene. Homozygous mice are viable, fertile and normal in size. Jip1 is normally expressed in neurons, the β cells of pancreatic islets, lung, and kidney. JIP1 protein also accumulates in the perinuclear region of hippocampal neurons following exposure to stress. The JIP group of scaffold proteins bind to c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase (MAPK) kinase 7 (MKK7), and to members of the mixed lineage protein kinase (MLK) group, and is required for stress induced activation of JNK in hippocampal neurons. The JNK signaling pathways are involved in the regulation of cellular proliferation, transformation, and apoptosis, and has been implicated in some neurodegenerative diseases, diabetes, and arthritis. JIP1 activation of JNK also leads to diet-induced obesity and insulin resistance. Deleting exon 3 of Jip1 in these mice, which encodes the JNK binding domain (JBD) of JIP1, results in reduced stress-induced lesions in the CA3 subfield of the hippocampus. These mice exhibited normal islet morphology, expression of insulin and glucagon, and blood glucose concentrations. These mice may be useful for studying MAP kinase signaling pathways and stress-induced activation of JNK.
A targeting vector was designed to replace exon 3 of the mitogen-activated protein kinase 8 interacting protein 1 (Mapk8ip1 or Jip1) gene with a neomycin resistance (neo) cassette in reverse orientation to the gene. 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 to C57BL/6J to generate a colony of Jip1- mice. These 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, Roger J Davis|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Mapk8ip1, mitogen-activated protein kinase 8 interacting protein 1|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||Exon 3, encoding the JNK-binding domain, was replaced with a neomycin selection cassette. Western blot analysis of brain tissue showed an absence of encoded protein in homozygous mutant mice.|
|Mutations Made By|| |
Roger Davis, University of Massachusetts Medical Sch.
When maintaining a live colony, homozygous mice may be bred together.
When using the B6.129S6-Mapk8ip1tm1Rjd/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #013535 in your Materials and Methods section.