Detection of the Onset of Ischemia and Carcinogenesis by Hypoxia-Inducible Transcription Factor-Based In Vivo Bioluminescence Imaging

An animal model for the early detection of common fatal diseases such as ischemic diseases and cancer is desirable for the development of new drugs and treatment strategies. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates oxygen homeostasis and plays key roles in a number of diseases, including cancer. Here, we established transgenic (Tg) mice that carry HRE/ODD-luciferase (HOL) gene, which generates bioluminescence in an HIF-1-dependent manner and was successfully used in this study to monitor HIF-1 activity in ischemic tissues. To monitor carcinogenesis in vivo, we mated HOL mice with rasH2 Tg mice, which are highly sensitive to carcinogens and are used for short-term carcinogenicity assessments. After rasH2-HOL Tg mice were treated with N-methyl-N-nitrosourea, bioluminescence was detected noninvasively as early as 9 weeks in tissues that contained papillomas and malignant lesions. These results suggest that the Tg mouse lines we established hold significant potential for monitoring the early onset of both ischemia and carcinogenesis and that these lines will be useful for screening chemicals for carcinogenic potential

PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice

A new mouse model of spontaneous autoimmune disease reveals an important role for the inhibitory co-receptor LAG-3 in suppressing autoimmunity

Longitudinal strain of right ventricular free wall by 2-dimensional speckle-tracking echocardiography is useful for detecting pulmonary hypertension

Aims Echocardiography is widely used for screening pulmonary hypertension (PH). More recently developed two-dimensional speckle-tracking echocardiography (2D-STE) can assess regional deformation of the myocardium and is useful for detecting left ventricular dysfunction. However, its usefulness to assess right ventricular (RV) dysfunction is not clear. Therefore, the aim of this study was to investigate the ability of peak systolic strain (PSS) and post-systolic strain index (PSI) at the RV free wall determined by 2D-STE to detect PH. Main methods Thirty-six images (27 images from PH patients, nine from patients with connective tissue disease without PH) obtained by 2D-STE were analysed. We investigated the relationship between RV hemodynamics measured by right heart catheterization and PSS, PSI and other echocardiographic parameters reflecting RV overload including RV end-diastolic diameter (RVDd) and tricuspid valve regurgitant pressure gradient (TRPG). Key findings PSS, PSI, RVDd and TRPG were all correlated with mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR). Furthermore, when PSS and MPAP were measured twice, the change in PSS was correlated with the change in MPAP (r = 0.633, p = 0.037). Multivariate logistic regression analysis identified PSS as the only independent factor associated with MPAP ? 35 mm Hg [odds ratio (OR), 1.616; 95% confidence interval (CI) 1.017-2.567; p = 0.042] and PVR ? 400 dyn・s・cm- 5(OR, 1.804; 95% CI 1.131-2.877; p = 0.013). Furthermore, the optimal PSS cut-off value to detect an elevated MPAP and PVR was - 20.75%, based on receiver operating characteristic curve analysis. Significance PSS of the RV free wall might serve as a useful non-invasive indicator of PH

Strain preservation of experimental animals: Vitrification of two-cell stage embryos for multiple mouse strains

AbstractStrain preservation of experimental animals is crucial for experimental reproducibility. Maintaining complete animal strains, however, is costly and there is a risk for genetic mutations as well as complete loss due to disasters or illness. Therefore, the development of effective vitrification techniques for cryopreservation of multiple experimental animal strains is important. We examined whether a vitrification method using cryoprotectant solutions, P10 and PEPeS, is suitable for preservation of multiple inbred and outbred mouse strains. First, we investigated whether our vitrification method using cryoprotectant solutions was suitable for two-cell stage mouse embryos. In vitro development of embryos exposed to the cryoprotectant solutions was similar to that of fresh controls. Further, the survival rate of the vitrified embryos was extremely high (98.1%). Next, we collected and vitrified two-cell stage embryos of 14 mouse strains. The average number of embryos obtained from one female was 7.3–33.3. The survival rate of vitrified embryos ranged from 92.8% to 99.1%, with no significant differences among mouse strains. In vivo development did not differ significantly between fresh controls and vitrified embryos of each strain. For strain preservation using cryopreserved embryos, two offspring for inbred lines and one offspring for outbred lines must be produced from two-cell stage embryos collected from one female. The expected number of surviving fetuses obtained from embryos collected from one female of either the inbred or outbred strains ranged from 2.9 to 19.5. The findings of the present study indicated that this vitrification method is suitable for strain preservation of multiple mouse strains