The Cre/loxP system has become an important tool in designing postintegrational switch mechanisms for transgenes in mice. The power and spectrum of application of this system depends on transgenic mouse lines that provide Cre recombinase activity with a defined cell type-, tissue-, or developmental stage-specificity. We have developed a novel mouse line that acts as a Cre reporter. The mice, designated Z/EG (lacZ/EGFP), express lacZ throughout embryonic development and adult stages. Cre excision, however, removes the lacZ gene, which activates expression of the second reporter, enhanced green fluorescent protein. We have found that the double-reporter Z/EG line is able to indicate the occurrence of Cre excision from early embryonic to adult lineages. The advantage of the Z/EG line is that Cre-mediated excision can be monitored in live samples and that live cells with Cre-mediated excision can be isolated using a single-step FACS. It will be a valuable reagent for the increasing number of investigators taking advantage of the powerful tools provided by the Cre/loxP site-specific recombinase system.

IMPORTANCE Blood pressure (BP) is a known risk factor for overall mortality and cardiovascular (CV)-specific fatal and nonfatal outcomes. It is uncertain which BP index is most strongly associated with these outcomes.OBJECTIVE To evaluate the association of BP indexes with death and a composite CV event.

The Cre/loxP system has become an important tool in designing postintegrational switch mechanisms for transgenes in mice. The power and spectrum of application of this system depends on transgenic mouse lines that provide Cre recombinase activity with a defined cell type-, tissue-, or developmental stage-specificity. We have developed a novel mouse line that acts as a Cre reporter. The mice, designated Z/EG (lacZ/EGFP), express lacZ throughout embryonic development and adult stages. Cre excision, however, removes the lacZ gene, which activates expression of the second reporter, enhanced green fluorescent protein. We have found that the double-reporter Z/EG line is able to indicate the occurrence of Cre excision from early embryonic to adult lineages. The advantage of the Z/EG line is that Cre-mediated excision can be monitored in live samples and that live cells with Cre-mediated excision can be isolated using a single-step FACS. It will be a valuable reagent for the increasing number of investigators taking advantage of the powerful tools provided by the Cre/loxP site-specific recombinase system.

Insulin-like growth factor-binding protein 7 (IGFBP7) is a secreted factor that suppresses growth, and the abundance of IGFBP7 inversely correlates with tumor progression. Here, we showed that pretreatment of normal and breast cancer cells with IGFBP7 interfered with the activation and internalization of insulin-like growth factor 1 receptor (IGF1R) in response to insulin-like growth factors 1 and 2 (IGF-1/2), resulting in the accumulation of inactive IGF1R on the cell surface and blockade of downstream phosphatidylinositol 3-kinase (PI3K)-AKT signaling. Binding of IGFBP7 and IGF-1 to IGF1R was mutually exclusive, and the N-terminal 97 amino acids of IGFBP7 were important for binding to the extracellular portion of IGF1R and for preventing its activation. Prolonged exposure to IGFBP7 resulted in activation of the translational repressor 4E-binding protein 1 (4E-BP1) and enhanced sensitivity to apoptosis in IGF1R-positive cells. These results support a model whereby IGFBP7 binds to unoccupied IGF1R and suppresses downstream signaling, thereby inhibiting protein synthesis, cell growth, and survival.