Project description:We assigned carboxypeptidase X 2 (Cpxm2) to a genetic locus for left ventricular mass. The functional role of Cpxm2 was investigated in Cpxm2-deficient (KO) and wild-type (WT) mice exposed to deoxycorticosterone acetate (DOCA)-salt hypertension and control conditions (SHAM). Both WT and KO animals developed severe and similar systolic hypertension in response to DOCA. WT mice developed severe LV damage. These changes were significantly ameliorated or even normalized (i.e. ejection fraction) in KO-DOCA animals. LV transcriptome analysis in WT, but not in KO mice, showed a molecular cardiac hypertrophy/remodeling signature with significant upregulation of 1234 transcripts including Cpxm2 in response to DOCA.
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:To understand the mechanisms through which JunB regulates Tregs-mediated immune regulation, we examined the global gene expression profiles in the JunB WT and KO Tregs by performing RNA sequencing (RNA-seq) analysis.
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:Background: Neuron-expressing ADAM17 (a disintegrin and metalloprotease 17) has been shown to support sympatho-excitation and salt-sensitive hypertension. The aim of current work was to identify by what mechanism ADAM17 in glutamatergic neurons support activation of presympathetic neurons (PSN). Methods: Both acute Ang-II stimulation in the PVN (paraventricular nucleus) and DOCA (deoxycorticosterone acetate)-salt model were utilized for electrophysiological recording and blood pressure (BP) recording, in mice with ADAM17 selective knockout in glutamatergic neurons (A17G), and ADAM17 targeted knockout in certain glutamatergic PVN-RVLM (rostral ventrolateral medulla) projecting neurons (PSN-A17G). Results: Both Ang-II and DOCA-salt treatment markedly decreased GABAergic inhibitory tone in the PVN of WT (wild-type) mice. Post DOCA-salt treatment, microglia were activated in the PVN, with significantly more expression of CD68 and related cytokines. With 7-day of DOCA-salt treatment, before BP arrived its plateau, PVN microglia had already been activated, and they were spotted more closely to virus-labeled glutamatergic PSN. Moreover, the number of GABAergic presynaptic terminals, locating on the soma area of PSN, was markedly reduced. In both A17G and PSN-A17G, these DOCA-salt-associated changes were blunted. Further experiments revealed that Ang-II promotes neuron-mediated chemotaxis for microglia, and this effect in neurons involved ADAM17 and its downstream – CX3CL1/CX3CR1 chemotactic pathway. Pharmacologically blocking CX3CR, or inhibiting migration of microglia, confirmed the contribution of CX3CL1/CX3CR1 signaling pathway and microglial displacement to Ang-II-induced disinhibition and activation of PSN.
Project description:We report the transcriptomic analysis of RNA-seq of abdominal aortas isolated from WT and PSGL-1-/- mice exposed to deoxycorticosterone acetate (DOCA) plus salt to uncover the mechanisms underlying the undefined role of PSGL-1 in abdominal aortic aneurysm (AAA)
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.
