The success of Cre-mediated conditional gene targeting depends on the specificity of Cre recombinase expression in Cre-transgenic mouse lines. As a tool to evaluate the specificity of Cre expression, we developed a reporter transgenic mouse strain that expresses enhanced green fluorescent protein (EGFP) upon Cre-mediated recombination. We demonstrate that the progeny resulting from a cross between this reporter strain and a transgenic strain expressing Cre in zygotes show ubiquitous EGFP fluorescence. This reporter strain should be useful to monitor the Cre expression directed by various promoters in transgenic mice, including mice in which Cre is expressed transiently during embryogenesis under a developmentally regulated promoter.z 2000 Federation of European Biochemical Societies.

The use of thoracic endovascular aortic repair alone for AEF should not be considered a definitive surgery. In contrast, esophagectomy, open surgery with aortic replacement using prostheses and homografts and greater omentum wrapping significantly improve the mid-term survival of AEF.

UMIN000018135.

-Thoracic aortic aneurysm (TAA) and dissection (TAD) are fatal diseases, which cause aortic rupture and sudden death. The small GTP-binding protein GDP dissociation stimulator (SmgGDS) is a crucial mediator of the pleiotropic effects of statins. Previous studies revealed that reduced force generation in AoSMCs causes TAA and TAD. -To examine the role of SmgGDS in TAA formation, we employed an angiotensin II (AngII, 1,000 ng/min/kg, 4 weeks)-induced TAA model. -33% mice died suddenly due to TAA rupture, whereas there was no TAA rupture in control mice. In contrast, there was no significant difference in the ratio of abdominal aortic aneurysm rupture between the two genotypes. We performed ultrasound imaging every week to follow the serial changes in aortic diameters. The diameter of the ascending aorta progressively increased in mice compared with mice, whereas that of the abdominal aorta remained comparable between the two genotypes. Histological analysis of mice showed dissections of major thoracic aorta in the early phase of AngII infusion (day 3~5) and more severe elastin degradation compared with mice. Mechanistically, mice showed significantly higher levels of oxidative stress, matrix metalloproteinases, and inflammatory cell migration in the ascending aorta compared with mice. For mechanistic analyses, we primary cultured aortic smooth muscle cells (AoSMCs) from the 2 genotypes. After AngII (100 nM) treatment for 24 hours, AoSMCs showed significantly increased MMP activity and oxidative stress levels compared with AoSMCs. In addition, SmgGDS deficiency increased cytokines/chemokines and growth factors in AoSMCs. Moreover, expressions of and, which are force generation genes, were significantly reduced in AoSMCs compared with AoSMCs. Similar tendency was noted in AoSMCs from TAA patients compared with those from controls. Finally, local delivery of the SmgGDS gene construct reversed the dilation of the ascending aorta in mice. -These results suggest that SmgGDS is a novel therapeutic target for the prevention and treatment of TAA.