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 JIP1TA 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.
