In this strain, a neomycin resistance cassette replaces exon 1 of the endogenous mitogen-activated protein kinase 8 interacting protein 3 (Mapk8ip3 or Jip3) gene, abolishing gene function. These mice may be useful for studying MAP kinase signaling pathways, neuronal organization and signaling, and JNK activation and regulation.
Roger J Davis, University of Massachusetts Medical Sch.
In this strain, a neomycin resistance cassette replaces exon 1 of the endogenous mitogen-activated protein kinase 8 interacting protein 3 (Mapk8ip3 or Jip3) gene, abolishing gene function. Heterozygous mice are viable, fertile, and normal in size, while homozygous mice die shortly after birth due to inability to breathe. Jip3 is both a scaffold protein and an adapter protein for cargo transport on microtubules, and is expressed in neurons. JIP3 binds preferentially to c-Jun N-terminal kinase 3 (JNK3), mitogen-activated protein kinase (MAPK) kinase 7 (MKK7), and to members of the mixed lineage protein kinase (MLK) group. 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. Although the brains of homozygotes are smaller when compared to WT littermates, they have similar morphology including the ependymal linings, neuronal rests, neuronal layers, and glial cell densities. The brains of mutants also exhibit significant bilateral defects in the telencephalon commissure and adjacent white matter, and in neuronal organization. Disruption of Jip3 expression results in changes in neuronal gene expression. Specifically, these mice exhibit decreased expression of rhodopsin guanine-nucleotide exchange factor (Rho-GEF) neuroepithelial cell transforming gene 1 (Net1) and the Rho-associated coiled-coil containing protein kinase (ROCK). There is also a decrease in the expression of a number of glutamate receptor subunits, however no defect in JNK activation was evident. These mice may be useful for studying MAP kinase signaling pathways, neuronal organization and signaling, and JNK activation and regulation.
A targeting vector was designed to replace exon 1 of the mitogen-activated protein kinase 8 interacting protein 3 (Mapk8ip3 or Jip3) gene with a neomycin resistance (neo) cassette. 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 Jip3- 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||Mapk8ip3, mitogen-activated protein kinase 8 interacting protein 3|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||Exon 1 was replaced by a neomycin resistance cassette. Northern blot analysis demonstrated the loss of the transcript. This was confirmed by immunoblot analysis demonstrating the loss of the protein.|
|Mutations Made By|| |
Roger Davis, University of Massachusetts Medical Sch.
When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony or C57BL/6J inbred mice (Stock No. 000664). Homozygous mice die shortly after birth.
When using the B6.129S6-Mapk8ip3tm1Rjd/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #013537 in your Materials and Methods section.