Project description:TDP-43-coding mutations are found among ALS patients. In oder to express human mutant TDP-43 protein in the mouse under the control of the endogenous Tardp promoter, we have generate a mouse line wit 300% elevated TDP-43 level.
Project description:TDP-43-coding mutations are found among ALS patients. In oder to express human mutant TDP-43 protein in the mouse under the control of the endogenous Tardp promoter, we have generate a mouse line wit 300% elevated TDP-43 level. Total RNA obtained from 4-6 male mutant mice was compared to 4-6 wild type controls.
Project description:Hepatosteatosis underlies several diseases including type 2 diabetes, cardiovascular disease and liver disease. Unfortunately, our understanding of the contributing pathways that initiate and advance hepatosteatosis to subsequent complications is still poorly understood. Here, we take advantage of recent developments in “omics” technologies to perform high resolution proteomics (>5000 proteins) and quantitative lipidomics (>300 lipids) on livers from 107 genetically diverse inbred mouse strains from the hybrid mouse diversity panel. Integration of these data allowed us to define novel regulators of lipid metabolism in the liver.
Project description:Hepatosteatosis underlies several diseases including type 2 diabetes, cardiovascular disease and liver disease. Unfortunately, our understanding of the contributing pathways that initiate and advance hepatosteatosis to subsequent complications is still poorly understood. Here, we take advantage of recent developments in “omics” technologies to perform high resolution proteomics (>5000 proteins) and quantitative lipidomics (>300 lipids) on livers from 107 genetically diverse inbred mouse strains from the hybrid mouse diversity panel. Integration of these data allowed us to define novel regulators of lipid metabolism in the liver.
Project description:In the present study, genomic binding sites of glucocorticoid receptors (GR) were identified in vivo in the rat hippocampus applying chromatin immunoprecipitation followed by next-generation sequencing. We identified 2470 significant GR-binding sites (GBS) and were able to confirm GR binding to a random selection of these GBS covering a wide range of P values. Analysis of the genomic distribution of the significant GBS revealed a high prevalence of intragenic GBS. Gene ontology clusters involved in neuronal plasticity and other essential neuronal processes were overrepresented among the genes harboring a GBS or located in the vicinity of a GBS. Male adrenalectomized rats were challenged with increasing doses of the GR agonist corticosterone (CORT) ranging from 3 to 3000 μg/kg, resulting in clear differences in the GR-binding profile to individual GBS. Two groups of GBS could be distinguished: a low-CORT group that displayed GR binding across the full range of CORT concentrations, and a second high-CORT group that displayed significant GR binding only after administering the highest concentration of CORT. All validated GBS, in both the low-CORT and high-CORT groups, displayed mineralocorticoid receptor binding, which remained relatively constant from 30 μg/kg CORT upward. Motif analysis revealed that almost all GBS contained a glucocorticoid response element resembling the consensus motif in literature. In addition, motifs corresponding with new potential GR-interacting proteins were identified, such as zinc finger and BTB domain containing 3 (Zbtb3) and CUP (CG11181 gene product from transcript CG11181-RB), which may be involved in GR-dependent transactivation and transrepression, respectively. In conclusion, our results highlight the existence of 2 populations of GBS in the rat hippocampal genome. - See more at: http://press.endocrine.org/doi/10.1210/en.2012-2187?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed#sthash.LqK088DP.dpuf
2016-07-09 | GSE84202 | GEO
Project description:Genetic Diversity and Environmental Adaptation in Ethiopian Tef