Overview

In this strain, codon 103 in exon 3 of the endogenous mitogen-activated protein kinase 8 interacting protein 1 (Mapk8ip1 or Jip1) gene is mutated from a Threonine (ACT) to an Alanine (GCC). These mice may be useful for studying MAP kinase signaling pathways and activation of JNK in response to metabolic stress.

Donating Investigator

Roger J Davis, University of Massachusetts Medical Sch.

Genetic overview

Genetic Background	Generation

Mapk8ip1^tm3.1Rjd

Allele Type	Gene Symbol	Gene Name
Targeted (Not Specified)	Mapk8ip1	mitogen-activated protein kinase 8 interacting protein 1

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Research Applications

Neurobiology Research
Diabetes and Obesity Research
Apoptosis Research
Cell Biology Research
Immunology, Inflammation and Autoimmunity Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

In this strain, codon 103 in exon 3 of the endogenous mitogen-activated protein kinase 8 interacting protein 1 (Mapk8ip1 or Jip1) gene was mutated from a Threonine (ACT) to an Alanine (GCC). Homozygous mice are viable, fertile, and normal in size. Jip1 is expressed in neurons, the β cells of pancreatic islets, lung, and kidney.
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 JNK activation. Phosphorylation of codon 103 is essential for JIP1 to activate JNK, which results in diet-induced obesity and insulin resistance. The loss of JIP1-mediated JNK activation in these JIP1^TA mice results in increased insulin sensitivity and fat oxidation when fed a high fat diet (HFD). These mice also exhibit a decrease in hepatic glucose production, accumulation of hepatic lipids and triglycerides. Hyperglycemia, hyperinsulinemia, and food intake are reduced. No difference in weight gain, glucose intolerance, glucose-induced insulin release, insulin-stimulated whole-body glucose turnover, glycoloysis, or glycogen synthesis is observed when compared to wildtype mice on a HFD. These mice may be useful for studying MAP kinase signaling pathways and activation of JNK in response to metabolic stress.

Development

A targeting construct was made containing exon 3 of the mitogen-activated protein kinase 8 interacting protein 1 (Mapk8ip1 or Jip1) gene. Codon 103 in exon 3 was mutated from a Threonine (ACT) to an Alanine (GCC), and a loxP-flanked neomycin (neo) resistance cassette was placed downstream of exon 3. 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 Jip1^TA 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.

Control Suggestions

Wild-type from the colony

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Morel C; Standen CL; Jung DY; Gray S; Ong H; Flavell RA; Kim JK; Davis RJ. 2010. Requirement of JIP1-Mediated c-Jun N-Terminal Kinase Activation for Obesity-Induced Insulin Resistance. Mol Cell Biol 30(19):4616-25PubMed: 20679483 MGI: J:163808

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Genetics

Mapk8ip1^tm3.1Rjd

Allele Symbol: Mapk8ip1^tm3.1Rjd

Allele Name	targeted mutation 3.1, Roger J Davis
Allele Type	Targeted (Not Specified)
Allele Synonym(s)	Mapk8ip1^T103A
Gene Symbol and Name	Mapk8ip1, mitogen-activated protein kinase 8 interacting protein 1
Gene Synonym(s)
Promoter	Mapk8ip1, mitogen-activated protein kinase 8 interacting protein 1, mouse, laboratory
Strain of Origin	129S6/SvEvTac
Chromosome	2
Molecular Note	A targeting construct was made containing exon 3 of the mitogen-activated protein kinase 8 interacting protein 1 (Mapk8ip1 or Jip1) gene. Codon 103 in exon 3 was mutated from a Threonine (ACT) to an Alanine (GCC) (T103A), and a loxP-flanked neomycin (neo) resistance cassette was placed downstream of exon 3. Cre mediated recombination removed the neo cassette.
Mutations Made By	Roger Davis, University of Massachusetts Medical Sch.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Neurobiology Research
- Neurodegeneration
- Parkinson's Disease
- Huntington's disease
- Alzheimer's Disease
Diabetes and Obesity Research
Apoptosis Research
Cell Biology Research
- Genes Regulating Growth and Proliferation
- Signal Transduction
Immunology, Inflammation and Autoimmunity Research
- Intracellular Signaling Molecules

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Mapk8ip1^tm3.1Rjd/Mapk8ip1^tm3.1Rjd
B6.129S6-Mapk8ip1

behavior/neurological phenotype

decreased food intake
- modestly in mice fed a high fat diet

homeostasis/metabolism phenotype

abnormal gluconeogenesis
- during hyperinsulinemic-euglycemic clamp studies, mice fed a normal or high fat diet exhibit increased insulin-mediated suppression of hepatic glucose production compared with similarly treated wild-type mice
- Normal - however, basal hepatic glucose production is normal

decreased circulating leptin level
- in mice fed a high fat diet

decreased liver triglyceride level
- mice fed a high fat diet exhibit less increase in liver triglyceride compared with similarly treated wild-type mice

decreased respiratory quotient
- whether mice are fed a standard or high fat diet

increased insulin sensitivity
- mice fed a high fat diet exhibit greater steady-state glucose infusion rates during hyperinsulinemic-euglycemic clamp studies compared with similarly treated wild-type mice
- when mice are fed a high fat diet, insulin-induced disposal of blood glucose is increased compared to in similarly treated wild-type mice

liver/biliary system phenotype

abnormal liver morphology
- mice fed a high fat diet exhibit reduced morphological changes, increase in mass, and accumulation of triglycerides compared with wild-type mice

decreased liver triglyceride level
- mice fed a high fat diet exhibit less increase in liver triglyceride compared with similarly treated wild-type mice

decreased liver weight
- mice fed a high fat diet exhibit less increase in liver mass compared with similarly treated wild-type mice

decreased susceptibility to hepatic steatosis
- in mice fed a high fat diet

References

Morel C; Standen CL; Jung DY; Gray S; Ong H; Flavell RA; Kim JK; Davis RJ. 2010. Requirement of JIP1-Mediated c-Jun N-Terminal Kinase Activation for Obesity-Induced Insulin Resistance. Mol Cell Biol 30(19):4616-25PubMed: 20679483 MGI: J:163808

Additional - Mapk8ip1^tm3.1Rjd related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Mapk8ip1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, homozygous mice may be bred together.
- Additional Breeding and Husbandry Support
Citation
When using the B6.129-Mapk8ip1^tm3.1Rjd/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #013536 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or wildtype for Mapk8ip1<tm3.1Rjd>

Related Products and Services

Frozen Mouse Embryo	B6.129-Mapk8ip1<tm3.1Rjd>/J	$2595.00
Frozen Mouse Embryo	B6.129-Mapk8ip1<tm3.1Rjd>/J	$2595.00
Frozen Mouse Embryo	B6.129-Mapk8ip1<tm3.1Rjd>/J	$3373.50
Frozen Mouse Embryo	B6.129-Mapk8ip1<tm3.1Rjd>/J	$3373.50

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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General Terms and Conditions

Questions about Terms of Use

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Licensing Information

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Mapk8ip1tm3.1Rjd

Allele Symbol: Mapk8ip1tm3.1Rjd

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Mapk8ip1tm3.1Rjd/Mapk8ip1tm3.1RjdB6.129S6-Mapk8ip1

behavior/neurological phenotype

homeostasis/metabolism phenotype

liver/biliary system phenotype

References

Additional - Mapk8ip1tm3.1Rjd related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Mapk8ip1^tm3.1Rjd

Allele Symbol: Mapk8ip1^tm3.1Rjd

Genotype: Mapk8ip1^tm3.1Rjd/Mapk8ip1^tm3.1Rjd
B6.129S6-Mapk8ip1

Additional - Mapk8ip1^tm3.1Rjd related