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In research into type 2 diabetes, diet-based approaches, i.e., nutritional intake, are important approaches for therapeutic research. We would like to make the following two proposals from the standpoint of laboratory animal science for reproducible animal studies using type 2 diabetes mouse models. These include congenic strains of diabetes mouse models and improvement of diets used in daily care and management. In this research, the Irs2homo-knockout mouse with both impaired glucose tolerance and insulin resistance, and thus type 2 diabetes, was established as a congenic strain. The effect of the genetic background on the onset of diabetes was examined. Next, we discussed which diets are appropriate for general care and management of mouse models in which the pathophysiology is controlled by nutritional conditions. Therefore, we prepared diets by converting the current Japanese and US diets to mice and adjusting the diet contents accordingly. We compared the insulin signals such as those of the liver, pancreas and white fat. We were thus able to establish an evaluation system closer to diabetes in the current population. Using this data as an example, we should consider the quality and ordinary diet of animals as important factors in animal experiments. Source

Sasaki E.,Keio University | Sasaki E.,Central Institute for Experimental Animals
Neuroscience Research | Year: 2015

Genetically modified mice have contributed much to studies in the life sciences. In some research fields, however, mouse models are insufficient for analyzing the molecular mechanisms of pathology or as disease models. Often, genetically modified non-human primate (NHP) models are desired, as they are more similar to human physiology, morphology, and anatomy. Recent progress in studies of the reproductive biology in NHPs has enabled the introduction of exogenous genes into NHP genomes or the alteration of endogenous NHP genes. This review summarizes recent progress in the production of genetically modified NHPs, including the common marmoset, and future perspectives for realizing genetically modified NHP models for use in life sciences research. © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. Source

Oshima H.,Kanazawa University | Hioki K.,Central Institute for Experimental Animals | Popivanova B.K.,Kanazawa University | Oguma K.,Kanazawa University | And 3 more authors.
Gastroenterology | Year: 2011

Background & Aims Helicobacter pylori infection induces an inflammatory response, which can contribute to gastric tumorigenesis. Induction of cyclooxygenase-2 (COX-2) results in production of prostaglandin E2 (PGE2), which mediates inflammation. We investigated the roles of bacterial infection and PGE2 signaling in gastric tumorigenesis in mice. Methods We generated a germfree (GF) colony of K19-Wnt1/C2mE mice (Gan mice); these mice develop gastric cancer. We examined tumor phenotypes, expression of cytokines and chemokines, and recruitment of macrophages. We also investigated PGE2 signaling through the PGE2 receptor subtype 4 (EP4) in Gan mice given specific inhibitors. Results Gan mice raised in a specific pathogen-free facility developed large gastric tumors, whereas gastric tumorigenesis was significantly suppressed in GF-Gan mice; reconstitution of commensal flora or infection with Helicobacter felis induced gastric tumor development in these mice. Macrophage infiltration was significantly suppressed in the stomachs of GF-Gan mice. Gan mice given an EP4 inhibitor had decreased expression of cytokines and chemokines. PGE2 signaling and bacterial infection or stimulation with lipopolysaccharide induced expression of the chemokine C-C motif ligand 2 (CCL2) (which attracts macrophage) in tumor stromal cells or cultured macrophages, respectively. CCL2 inhibition suppressed macrophage infiltration in tumors, and depletion of macrophages from the tumors of Gan mice led to signs of tumor regression. Wnt signaling was suppressed in the tumors of GF-Gan and Gan mice given injections of tumor necrosis factor-α neutralizing antibody. Conclusions Bacterial infection and PGE2 signaling are required for gastric tumorigenesis in mice; they cooperate to up-regulate CCL2, which recruits macrophage to gastric tumors. Macrophage-derived tumor necrosis factor-α promotes Wnt signaling in epithelial cells, which contributes to gastric tumorigenesis. © 2011 AGA Institute. Source

Central Institute For Experimental Animals | Date: 2013-09-20

The present invention provides an immunodeficient mouse (NOG mouse) suitable for engraftment, differentiation and proliferation of heterologous cells, and a method of producing such a mouse. This mouse is obtained by backcrossing a C.B-17-scid mouse with an NOD/Shi mouse, and further backcrossing an interleukin 2-receptor -chain gene-knockout mouse with the thus backcrossed mouse. It is usable for producing a human antibody and establishing a stem cell assay system, a tumor model and a virus-infection model.

Eto T.,Central Institute for Experimental Animals
Cryo letters | Year: 2015

OBJECTIVE: We examined whether the vitrification method using P10 and PEPeS is suitable for the cryopreservation of two-cell stage embryos collected from multiple rat strains with the objective of strain preservation of inbred rat strains.RESULTS: The average numbers of two-cell stage embryos collected per female for F344/Jcl, ACI/N, BUF/N, and WKY/N strains were 7.0 to 12.0, and survival rates of the embryos after vitrification were 94.2 to 96.3 % The in vitro development rates of vitrified embryos transferred were 47.1 to 60.8 %.CONCLUSION: At least two offspring produced from the embryos collected from one female are required for strain preservation of inbred strain. Taken together, the results of the experiment indicated expected numbers of surviving fetuses for embryos collected from one female were 3.2 to 6.7, and all were usable for strain preservation. The results suggest that this vitrification method is suitable for strain preservation of multiple inbred rat strains. Source

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