The Animal Research Facility of the National Institute of Public Health and the Environment (RIVM, The Netherlands) has successfully conducted several longevity and cross sectional studies with mice having a defect in DNA repair and/or RNA transcription. Some of these mouse strains showed phenotypes of accelerated aging. As part of the present program renewal application the animal and pathology core will continue to conduct those studies, but will now have a more specific focus (based on the results obtained in the previous grant period) and will include intervention studies. On the basis of results that will come out of the 4 projects, strategies will be developed to decrease oxidative DNA damage (considered as a main driving force in aging) in the mouse, using various modes of antioxidant and/or genome maintenance interventions. Overall, the specific aims of the animal/pathology core are: 1) to ensure uniformity and homogeneity of animals and the environment in which the animals will be housed; consequently the animals are (or will be) backcrossed into the same genetic C57BL/6 background. 2) to ensure that the animals are raised in a pathogen free environment; 3) to facilitate the sharing of animals and tissues or cells from them between the individual investigators; 4) to conduct longevity and/or cross sectional studies with Xpc, Erccl, Ku70, Ku80, Rad54/54B mice or mouse strains with combined DNA repair deficiencies, like Ttd/Ku80 (in total 15 studies); 5) to conduct life extension and exposure studies with Erccl mice (7 studies); 6) to conduct full histopathology on all animals from the longevity studies and if necessary also on mice from the cross sectional studies; 7) to set up strategies to include new mouse models in the life span and intervention studies on the basis of the results obtained in the 4 projects To make mutagenesis studies possible, all transgenic mouse lines will be crossed with lacZ containing pUR288 transgenic mice (see also studies as described in project 2).
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