Fol. Biol. 2017, 63, 67-77

https://doi.org/10.14712/fb2017063020067

Spontaneously Hypertensive Rat Chromosome 2 with Mutant Connexin 50 Triggers Divergent Effects on Metabolic Syndrome Components

Ondřej Šeda1, D. Křenová1, L. Šedová1, L. Kazdová2, M. Krupková1, B. Chylíková1, F. Liška1, V. Křen1

1Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
2Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

Received November 2016
Accepted February 2017

Metabolic syndrome is a frequent condition with multifactorial aetiology. Previous studies indicated the presence of genetic determinants of metabolic syndrome components on rat chromosome 2 (RNO2) and syntenic regions of the human genome. Our aim was to further explore these findings using novel rat models. We derived the BN-Dca and BN-Lx.Dca congenic strains by introgression of a limited RNO2 region from a spontaneously hypertensive rat strain carrying a mutation in the Gja8 gene (SHR-Dca, dominant cataract) into the genomic background of Brown Norway strain and congenic strain BN-Lx, respectively. We compared morphometric, metabolic and cytokine profiles of adult male BN-Lx, BN-Dca and BN-Lx.Dca rats. We performed in silico comparison of the DNA sequences throughout RNO2 differential segments captured in the new congenic strains. Both BN-Dca and BN-Lx.Dca showed lower total triacylglycerols and cholesterol concentrations compared to BN-Lx. Fasting insulin in BN-Dca was higher than in BN-Lx.Dca and BN-Lx. Concentrations of several proinflammatory cytokines were elevated in the BN-Dca strain, including IL-1α, IL-1β, IFN-γ and MCP-1. In silico analyses revealed over 740 DNA variants between BN-Lx and SHR genomes within the differential segment of the congenic strains. We derived new congenic models that prove that a limited genomic region of SHR-Dca RNO2 significantly affects lipid levels and insulin sensitivity in a divergent fashion.

Funding

This work was supported by Czech Science Foundation Projects 15-04871S and P301/12/0777, Project LK11217 from the Ministry of Education, Youth and Sports of the Czech Republic, and Charles University (PROGRES Q25, UNCE 204022).

References

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