Nucleoside diphosphate kinase 7, non-metastatic cells 7 (NME7) is an acknowledged member of ciliome and is involved in the biogenesis or function of cilia. As obesity and diabetes are common in several ciliopathies, we aimed to analyze changes of gene expression within Nme7 interactome in genetically designed rat models of metabolic syndrome. We assessed the liver transcriptome by Affymetrix microarrays in adult males of 14 PXO recombinant inbred rat strains and their two progenitor strains, SHR-Lx and BXH2. In the strains with the lowest expression of Nme7, we have identified significant enrichment of transcripts belonging to Nme7 interactome. In the subsequent network analysis, we have identified three major upstream regulators - Hnf4a , Ppara and Nr1h4 and liver steatosis (p=0.0001) and liver necrosis/cell death (apoptosis of liver cells, p=0.0003) among the most enriched Tox categories. The mechanistic network reaching the top score showed substantial overlap with Assembly of non-motile cilium and Glucose metabolism disorder gene lists. In summary, we show in a genetic model of metabolic syndrome that rat strains with the lowest expression of Nme7 present gene expression shifts of Nme7 interactome that are perturbing networks relevant for carbohydrate and lipid metabolism as well as ciliogenesis., L. Šedová, E. Školníková, M. Hodúlová, J. Včelák, O. Šeda, B. Bendlová., and Obsahuje bibliografii
The spontaneously hypertensive rat (SHR) is the most widely used animal model of essential hypertension an d accompanying metabolic disturbances. Recent advances in sequencing of genomes of BN- Lx and SHR progenitors of the BXH/HXB recombinant inbred (RI) strains as well as ac cumulation of multiple data sets of intermediary phenotypes in the RI strains, including mRNA and microRNA abundance, quantitative metabolomics, proteomics, methylomics or histone modifications, will make it possible to systematically search for genetic variants involved in regulation of gene ex pression and in the etiology of complex pathophysiological traits. New advances in manipulation of the rat genome, including e fficient transgenesis and gene targeting, will enable in vivo functional analys es of selected candidate genes to identify QTL at the molecular level or to provide insight into mechanisms whereby targeted genes affect pathophysiological traits in the SHR., M. Pravenec ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy