Conditional Transgenesis Using Dimerizable Cre (DiCre)

Cre recombinase is extensively used to engineer the genome of experimental animals. However, its usefulness is still limited by the lack of an efficient temporal control over its activity. We have recently developed a conceptually new approach to regulate Cre recombinase, that we have called Dimerizable Cre or DiCre. It is based on splitting Cre into two inactive moieties and fusing them to FKBP12 (FK506-binding protein) and FRB (binding domain of the FKBP12-rapamycin associated protein), respectively. These latter can be efficiently hetero-dimerized by rapamycin, leading to the reinstatement of Cre activity. We have been able to show, using in vitro approaches, that this ligand-induced dimerization is an efficient way to regulate Cre activity, and presents a low background activity together with a high efficiency of recombination following dimerization. To test the in vivo performance of this system, we have, in the present work, knocked-in DiCre into the Rosa26 locus of mice. To evaluate the performance of the DiCre system, mice have been mated with indicator mice (Z/EG or R26R) and Cre-induced recombination was examined following activation of DiCre by rapamycin during embryonic development or after birth of progenies. No recombination could be observed in the absence of treatment of the animals, indicating a lack of background activity of DiCre in the absence of rapamycin. Postnatal rapamycin treatment (one to five daily injection, 10 mg/kg i.p) induced recombination in a number of different tissues of progenies such as liver, heart, kidney, muscle, etc. On the other hand, recombination was at a very low level following in utero treatment of DiCre×R26R mice. In conclusion, DiCre has indeed the potentiality to be used to establish conditional Cre-deleter mice. An added advantage of this system is that, contrary to other modulatable Cre systems, it offers the possibility of obtaining regulated recombination in a combinatorial manner, i.e. induce recombination at any desired time-point specifically in cells characterized by the simultaneous expression of two different promoters

Dietary factors associated with metabolic syndrome and its components in overweight and obese Brazilian schoolchildren: a cross-sectional study

BACKGROUND: The metabolic syndrome (MS) has been assessed since childhood mainly because of the nutritional and epidemiological transition that has occurred worldwide. Our objectives were to explore the MS and its components according to anthropometric and demographic factors and to assess the relationship among MS components and dietary characteristics in overweight and obese schoolchildren. METHODS: This was a cross-sectional study which included 147 schoolchildren (aged 6–10 years) from three elementary schools, with body mass index (BMI) higher than the 85th percentile. Sexual maturation stages, anthropometric measures (weight, height, skinfold thickness and waist circumference), biochemical data (glucose, HDL-C and triacylglycerol), blood pressure and dietary intake were assessed. The metabolic syndrome was diagnosed if three or more of the following components were presented: waist circumference ≥90th age and sex-specific cut-off, blood pressure ≥90th age, sex and height-specific cut-off, glucose ≥100 mg/dL, HDL-C ≥ 40 mg/dL and triacylglycerols ≥ 110 mg/dL. The dietary intake was assessed by three non-consecutive 24-h recalls. The T test, Kruskal–Wallis and multiple linear regression analysis were applied to assess MS components and dietary intake. RESULTS: The MS percentage was 10.2 % and it was higher in obese children and ones with high body fat percentage. The waist circumference was the main altered component of MS and 62 % of overweight schoolchildren showed at least one altered component of MS. The components of metabolic syndrome associated with dietary intake were triacylglycerol (positive association with saturated and monounsaturated fat, whole-milk products and processed foods and negative associated with legumes and polyunsaturated fat), glycemia (positive association with processed foods and negative with cereals), HDL-C (positive association with vegetables and greens) and waist circumference was negative associated with protein. CONCLUSIONS: The frequency of MS was higher in obese than overweight schoolchildren and the frequency of at least one MS component was high in more than half of our subjects. The waist circumference was the most frequent among all other components. The triacylglycerol and glycemia were the most frequent MS components associated with dietary intake. Unprocessed food was considered a protective dietary factor for MS metabolic components and processed food with high percentage of sugar and saturated fat was a risk factor for MS metabolic components

Influence de la vitesse d'absorption des acides aminés sur leur bilan hépatique chez le veau préruminant

International audienc

Transport des acides aminés dans l'aire splanchnique par le plasma sanguin et le sang chez le veau préruminant

International audienc

Transport des acides aminés dans l'aire splanchnique par le plasma sanguin et le sang chez le veau préruminant

International audienc

Influence de la vitesse d'absorption des acides aminés sur leur bilan hépatique chez le veau préruminant

International audienc

Chronic and low doses exposure of environmental pollutants induces phenotypic alterations in a tumour progression model of breast cancer

International audienc