Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse   Donating Investigator Roger J Davis,   University of Massachusetts Medical Sch.

Description
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.

Development
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.

Related Strains

Strains carrying other alleles of Mapk8ip1

013536	B6.129-Mapk8ip1tm3.1Rjd/J
011019	B6.129S6-Mapk8ip1tm2.1Rjd/J

View Strains carrying other alleles of Mapk8ip1     (2 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Diabetes Mellitus, Noninsulin-Dependent; NIDDM   (MAPK8IP1)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Mapk8ip1^tm1Rjd/Mapk8ip1^tm1Rjd

        involves: 129S6/SvEvTac * C57BL/6

• nervous system phenotype
• abnormal NMDA-mediated synaptic currents
  • NMDA-mediated current amplitude is decreased relative to in wild-type mice   (MGI Ref ID J:125318)
• decreased susceptibility to neuronal excitotoxicity
  • in vitro, mutant hippocampal neurons exhibit reduced stress-induced apoptosis following exposure to the excitotoxin kainate   (MGI Ref ID J:77616)
  • mutant neurons are also resistant to the apoptotic effects of anoxic stress induced by oxygen-glucose deprivation, as shown by reduced labeling in TUNEL assays and increased cell survival   (MGI Ref ID J:77616)
  • following exposure to kainite-induced excitotoxic stress, mutant hippocampal neurons display attenuated JNK activation despite a normal level of Jun protein expression   (MGI Ref ID J:77616)
  • in vivo, homozygotes show a severe reduction in the extent of kainate-induced lesions in the CA3 subfield of the hippocampus, with a reduced distribution of TUNEL-positive and GFAP-positive astroglial fibers relative to wild-type mice   (MGI Ref ID J:77616)
  • no differences in JNK activation is observed following exposure to ultraviolet radiation or treatment with the drug anisomycin   (MGI Ref ID J:77616)
• homeostasis/metabolism phenotype
• *normal* homeostasis/metabolism phenotype
  • contrary to expectations, homozygotes display normal islet morphology, normal expression of insulin and glucagon, as well as normal blood glucose levels and performance in glucose tolerance tests relative to wild-type mice   (MGI Ref ID J:77616)
• • decreased susceptibility to neuronal excitotoxicity
    • in vitro, mutant hippocampal neurons exhibit reduced stress-induced apoptosis following exposure to the excitotoxin kainate   (MGI Ref ID J:77616)
    • mutant neurons are also resistant to the apoptotic effects of anoxic stress induced by oxygen-glucose deprivation, as shown by reduced labeling in TUNEL assays and increased cell survival   (MGI Ref ID J:77616)
    • following exposure to kainite-induced excitotoxic stress, mutant hippocampal neurons display attenuated JNK activation despite a normal level of Jun protein expression   (MGI Ref ID J:77616)
    • in vivo, homozygotes show a severe reduction in the extent of kainate-induced lesions in the CA3 subfield of the hippocampus, with a reduced distribution of TUNEL-positive and GFAP-positive astroglial fibers relative to wild-type mice   (MGI Ref ID J:77616)
    • no differences in JNK activation is observed following exposure to ultraviolet radiation or treatment with the drug anisomycin   (MGI Ref ID J:77616)
• cellular phenotype
• decreased susceptibility to neuronal excitotoxicity
  • in vitro, mutant hippocampal neurons exhibit reduced stress-induced apoptosis following exposure to the excitotoxin kainate   (MGI Ref ID J:77616)
  • mutant neurons are also resistant to the apoptotic effects of anoxic stress induced by oxygen-glucose deprivation, as shown by reduced labeling in TUNEL assays and increased cell survival   (MGI Ref ID J:77616)
  • following exposure to kainite-induced excitotoxic stress, mutant hippocampal neurons display attenuated JNK activation despite a normal level of Jun protein expression   (MGI Ref ID J:77616)
  • in vivo, homozygotes show a severe reduction in the extent of kainate-induced lesions in the CA3 subfield of the hippocampus, with a reduced distribution of TUNEL-positive and GFAP-positive astroglial fibers relative to wild-type mice   (MGI Ref ID J:77616)
  • no differences in JNK activation is observed following exposure to ultraviolet radiation or treatment with the drug anisomycin   (MGI Ref ID J:77616)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Apoptosis Research

Cell Biology Research
Genes Regulating Growth and Proliferation
Signal Transduction

Diabetes and Obesity Research

Immunology, Inflammation and Autoimmunity Research
Intracellular Signaling Molecules

Neurobiology Research
Alzheimer's Disease
Huntington's disease
Neurodegeneration
Parkinson's Disease

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Mapk8ip1tm1Rjd
Allele Name		targeted mutation 1, Roger J Davis
Allele Type		Targeted (knock-out)
Common Name(s)		Jip1-;
Mutation Made By		Roger Davis,   University of Massachusetts Medical Sch.
Strain of Origin		129S6/SvEvTac
Gene Symbol and Name		Mapk8ip1, mitogen-activated protein kinase 8 interacting protein 1
Chromosome		2
Gene Common Name(s)		IB1; JIP-1; JIP1; Mapk8ip; PRKM8IP; Prkm8ip; Skip; mjip-2a; protein kinase, mitogen-activated 8 interacting protein;
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. [MGI Ref ID J:77616]

Genotyping

Genotyping Information

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Whitmarsh AJ; Kuan CY; Kennedy NJ; Kelkar N; Haydar TF; Mordes JP; Appel M; Rossini AA; Jones SN; Flavell RA; Rakic P; Davis RJ. 2001. Requirement of the JIP1 scaffold protein for stress-induced JNK activation. Genes Dev 15(18):2421-32. [PubMed: 11562351]  [MGI Ref ID J:77616]

Additional References

Mapk8ip1^tm1Rjd related

Barnat M; Enslen H; Propst F; Davis RJ; Soares S; Nothias F. 2010. Distinct roles of c-Jun N-terminal kinase isoforms in neurite initiation and elongation during axonal regeneration. J Neurosci 30(23):7804-16. [PubMed: 20534829]  [MGI Ref ID J:160890]

Jaeschke A; Czech MP; Davis RJ. 2004. An essential role of the JIP1 scaffold protein for JNK activation in adipose tissue. Genes Dev 18(16):1976-80. [PubMed: 15314024]  [MGI Ref ID J:91841]

Kennedy NJ; Martin G; Ehrhardt AG; Cavanagh-Kyros J; Kuan CY; Rakic P; Flavell RA; Treistman SN; Davis RJ. 2007. Requirement of JIP scaffold proteins for NMDA-mediated signal transduction. Genes Dev 21(18):2336-46. [PubMed: 17875667]  [MGI Ref ID J:125318]

Standen CL; Kennedy NJ; Flavell RA; Davis RJ. 2009. Signal transduction cross talk mediated by Jun N-terminal kinase-interacting protein and insulin receptor substrate scaffold protein complexes. Mol Cell Biol 29(17):4831-40. [PubMed: 19564410]  [MGI Ref ID J:152617]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred together.

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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