B6.129-Mapk8ip1^tm3.1Rjd/J

Stock number: 013536
Research areas: Apoptosis Research, Cell Biology Research, Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research, Neurobiology Research

Description

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.

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.

Allele

Symbol: Mapk8ip1^tm3.1Rjd
Name: targeted mutation 3.1, Roger J Davis
MGI accession ID: MGI:4829783
Generation method: Targeted
Attributes: Not Specified
Marker symbol: Mapk8ip1
Marker name: mitogen-activated protein kinase 8 interacting protein 1
Chromosome: 2
Strain of origin: 129S6/SvEvTac
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.