To drive the expression of Cre recombinase, we Sipeimine demonstrated Cre-mediated loxP-dependent DNA recombination in the placenta but not in the maternal organs tested or in fetuses of transgenic mice. This double enhancer construct should be a useful genetic tool to manipulate placental gene expression in mice. This placenta expression vector should provide investigative opportunities to understand the functional role of specific genes in placental development and placenta-related pregnancy disorders. Quinidine Numerous earlier reports have attempted to identify and characterize placental gene regulatory elements. Several groups have used transgenic mouse approaches to show that a 5.4,6.0-kb promoter and 59-flanking sequence of HLA-G contains trophoblast-restricted regulatory elements. However, the level of reporter gene expression in transgenic placentas at day 12.5 was relatively low and 450 times less than endogenous bactin. Analysis of the murine Ada gene by Shi et al showed that a placenta regulatory element resided within a 1.8 kb segment of DNA in the 59 flanking region and that this element provided consistent but variable placenta-specific expression. A trophoblast specific enhancer derived from the 59 flanking region of the Tpbpa gene was also inconsistent in driving placenta specific expression in transgenic mice. Calzonetti et al showed that a 340 bp fragment provided placenta specific expression of a lacZ reporter gene in only 5 of 16 transgenic lines examined. In recent years, gene transfer strategies, aimed at targeting genes to the trophoblast lineages, have been used in efforts to overcome this limitation. For example, direct injection of gene-therapy vectors into placentas results in limited levels of gene expression in the placenta, but also results in serious injury and patchy expression. Trophoblast-specific gene manipulation using lentivirusbased vectors has recently been developed and used in mice and rats. However, the lentivirus-based vector mediated trophoblast-specific gene expression requires blastocyst isolation, incubation with lentivirus vectors and the microinjection of transduced blastocysts into pseudopregnant mice. This approach is expensive, time consuming and inconvenient for general laboratory use. Thus, development of efficient, noninvasive and convenient genetic tools to specifically manipulate gene expression in placenta is desperately needed and would greatly facilitate efforts to understand placental formation and fetal development. In order to construct a more robust and reliable placenta specific expression construct, we assembled a chimeric placental expression vector using placental enhancer elements from two genes, Tpbpa and Ada. Each of these genes has been previously characterized by prenatal expression in the placenta, with highest expression occurring in the spongiotrophoblast layer.