Pregnancy and helminth infections.

It has been proposed that helminth infection may be particularly detrimental during pregnancy, through adverse effects on maternal anaemia and on birth outcomes, and that anthelminthic treatment during pregnancy will therefore be particularly beneficial. However, the few treatment trials that have been conducted have given, but little support to this notion and further trials in settings of nutritional stress are needed. It has also been proposed that prenatal exposure to helminth infection has an important effect on the development of the foetal immune response. There is evidence that this may impact, long-term, upon responses to helminth and nonhelminth antigens, and to allergens. Exposure to helminths in utero may also have nonspecific effects that may modify the offspring's susceptibility to diseases mediated by inflammation, including metabolic disorders. The mechanisms of such effects are not known, but they deserve to be explored as current epidemiological findings suggest the possibility of primary prevention for inflammatory conditions such as allergy, through intervention during pregnancy

An Inducible and Reversible Mouse Genetic Rescue System

Inducible and reversible regulation of gene expression is a powerful approach for uncovering gene function. We have established a general method to efficiently produce reversible and inducible gene knockout and rescue in mice. In this system, which we named iKO, the target gene can be turned on and off at will by treating the mice with doxycycline. This method combines two genetically modified mouse lines: a) a KO line with a tetracycline-dependent transactivator replacing the endogenous target gene, and b) a line with a tetracycline-inducible cDNA of the target gene inserted into a tightly regulated (TIGRE) genomic locus, which provides for low basal expression and high inducibility. Such a locus occurs infrequently in the genome and we have developed a method to easily introduce genes into the TIGRE site of mouse embryonic stem (ES) cells by recombinase-mediated insertion. Both KO and TIGRE lines have been engineered for high-throughput, large-scale and cost-effective production of iKO mice. As a proof of concept, we have created iKO mice in the apolipoprotein E (ApoE) gene, which allows for sensitive and quantitative phenotypic analyses. The results demonstrated reversible switching of ApoE transcription, plasma cholesterol levels, and atherosclerosis progression and regression. The iKO system shows stringent regulation and is a versatile genetic system that can easily incorporate other techniques and adapt to a wide range of applications