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; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation +pN1 Generation Definitions   Donating Investigator Roger J Davis,   University of Massachusetts Medical Sch.

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 Information

	Control
	Wild-type from the colony
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Mapk8ip1

013535	B6.129S6-Mapk8ip1tm1Rjd/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^tm3.1Rjd/Mapk8ip1^tm3.1Rjd

        B6.129S6-Mapk8ip1^tm3.1Rjd

• 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   (MGI Ref ID J:163808)
  • however, basal hepatic glucose production is normal   (MGI Ref ID J:163808)
• decreased circulating leptin level
  • in mice fed a high fat diet   (MGI Ref ID J:163808)
• decreased liver triglyceride level
  • mice fed a high fat diet exhibit less increase in liver triglyceride compared with similarly treated wild-type mice   (MGI Ref ID J:163808)
• decreased respiratory quotient
  • whether mice are fed a standard or high fat diet   (MGI Ref ID J:163808)
• increased insulin sensitivity
  • when mice are fed a high fat diet, insulin-induced disposal of blood glucose is increased compared to in similarly treated wild-type mice   (MGI Ref ID J:163808)
  • 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   (MGI Ref ID J:163808)
• 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   (MGI Ref ID J:163808)
• • decreased liver triglyceride level
    • mice fed a high fat diet exhibit less increase in liver triglyceride compared with similarly treated wild-type mice   (MGI Ref ID J:163808)
  • decreased liver weight
    • mice fed a high fat diet exhibit less increase in liver mass compared with similarly treated wild-type mice   (MGI Ref ID J:163808)
  • decreased susceptibility to hepatic steatosis
    • in mice fed a high fat diet   (MGI Ref ID J:163808)
• behavior/neurological phenotype
• decreased food intake
  • modestly in mice fed a high fat diet   (MGI Ref ID J:163808)

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		Mapk8ip1tm3.1Rjd
Allele Name		targeted mutation 3.1, Roger J Davis
Allele Type		Targeted (knock-in)
Common Name(s)		Mapk8ip1T103A;
Mutation Made By		Roger Davis,   University of Massachusetts Medical Sch.
Strain of Origin		129S6/SvEvTac
Promoter		Mapk8ip1, mitogen-activated protein kinase 8 interacting protein 1, mouse, laboratory
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), and a loxP-flanked neomycin (neo) resistance cassette was placed downstream of exon 3. Cre mediated recombination removed the neo cassette. [MGI Ref ID J:163808]

Genotyping

Genotyping Information

Genotyping Protocols

Mapk8ip1^tm3.1Rjd, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

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):4616-25. [PubMed: 20679483]  [MGI Ref ID J:163808]

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.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

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.

---

Ordering Information
JAX^® Mice
Surgical and Preconditioning Services
JAX^® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.