Project description:In the present study we made use of the (1-renin) DOCA-salt mouse model - which has been previously shown to develop cardiac and renal hypertrophy - to evaluate the direct effects of high-salt diet on cardiac function and gene expression profiling. The comparison between low-salt and high-salt DOCA-treated mice will reveal what genes are directly modulated by sodium in (normotensive) DOCA-treated mice. Previous publications: Wang Q, Hummler E, Nussberger J, Clement S, Gabbiani G, Brunner HR, Burnier M. Blood pressure, cardiac, and renal responses to salt and deoxycorticosterone acetate in mice: role of renin genes. J Am Soc Nephrol. 2002;13:1509 –1516. Wang Q, Domenighetti AA, Pedrazzini T, Burnier M. Potassium supplementation reduces cardiac and renal hypertrophy independent of blood pressure in DOCA/salt mice. Hypertension. 2005 Sep;46(3):547-54. Keywords: comparative dose-response treatment (2 groups)
Project description:The aim of this study was to assess whether chronic treatment with RPV can modulate the progression of chronic liver disease, especially of non-alcoholic fatty liver disease (NAFLD), through a nutritional model in wild-type mice Mice were daily treated with RPV (p.o.) and fed with normal or high fat diet during 3 months to induce fatty liver disease
Project description:We compared the transcriptomic changes in cell populations of the arcuate nucleus of the hypothalamus in 21 day treated DOCA-salt male mice versus sham male mice using high-throughput single-nucleus RNA-seq.
Project description:The ketogenic diet has been successful in promoting weight loss among patients that have struggled with weight gain. This is due to the cellular switch in metabolism that utilizes liver-derived ketone bodies for the primary energy source rather than glucose. Fatty acid transport protein 2 (FATP2) is highly expressed in liver, small intestine, and kidney where it functions in both the transport of exogenous long chain fatty acids (LCFA) and in the activation to CoA thioesters of very long chain fatty acids (VLCFA). We have completed a multi-omic study of FATP2-null (Fatp2-/-) mice maintained on a ketogenic diet (KD) or paired control diet (CD), with and without a 24-hour fast (KD-fasted and CD-fasted) to address the impact of deleting FATP2 under high-stress conditions. Control (wt/wt) and Fatp2-/- mice were maintained on their respective diets for 4-weeks. Afterwards, half the population was sacrificed while the remaining were fasted for 24-hours prior to sacrifice. We then performed paired-end RNA-sequencing on the whole liver tissue to investigate differential gene expression. The differentially expressed genes mapped to ontologies such as the metabolism of amino acids and derivatives, fatty acid metabolism, protein localization, and components of the immune system’s complement cascade, and were supported by the proteome and histological staining.
Project description:The impact of high fat diet on secreted milk small RNA transcriptome was studied by isolating total RNA from milk fat fraction collected on lactation day 10 from control diet fed (C; n=5; 10% fat; 7% sucrose; Research Diets #D12450J, Brunswick, NJ) and high fat diet fed (HF; n=4; Research Diets #D12492, 60% of total kcal energy is fat and match 7% of total kcal is sucrose; Brunswick, NJ) mice.
Project description:The impact of high fat diet on secreted milk small RNA transcriptome was studied by isolating total RNA from milk fat fraction collected on lactation day 10 from control diet fed (C; n=5; 10% fat; 7% sucrose; Research Diets #D12450J, Brunswick, NJ) and high fat diet fed (HF; n=4; Research Diets #D12492, 60% of total kcal energy is fat and match 7% of total kcal is sucrose; Brunswick, NJ) mice.
Project description:Non-enzymatic activation of renin via its interaction with prorenin receptor (PRR) has been proposed as a key mechanism of local renin-angiotensin system (RAS) activation. The presence of renin and angiotensinogen has been reported in the rostral ventrolateral nucleus (RVLM). Overactivation of bulbospinal neurons RVLM is linked to hypertension (HTN). Previous studies have shown that the brain RAS plays a role in the pathogenesis of the deoxycorticosterone (DOCA)-salt HTN model. Thus, we hypothesized that PRR in the RVLM is involved in the local activation of the RAS, facilitating the development of DOCA-salt HTN. Selective PRR ablation targeting the RVLM (PRRRVLM-Null mice) resulted in an unexpected sex-dependent and biphasic phenotype in DOCA-salt HTN. That is, PRRRVLM-Null females (but not males) exhibited a significant delay in achieving maximal pressor responses during the initial stage of DOCA-salt HTN. Female PRRRVLM-Null subsequently showed exacerbated DOCA-salt-induced pressor responses during the “maintenance” phase with a maximal peak at 13 days on DOCA-salt. This exacerbated response was associated with an increased sympathetic drive to the resistance arterioles and the kidney, exacerbated fluid and sodium intake and output in response to DOCA-salt, and induced mobilization of fluids from the intracellular to extracellular space concomitant with elevated vasopressin. Ablation of PRR suppressed genes involved in RAS activation and catecholamine synthesis in the RVLM but also induced expression of genes involved in inflammatory responses. This study illustrates complex and sex-dependent roles of PRR in the neural control of BP and hydromineral balance through autonomic and neuroendocrine systems.
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.