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Characterization of the genomic structure and function of regions influencing renin and angiogenesis in the SS rat. Physiol Genomics 2011 Jul 14;43(13):808-17 PMID: 21521778 PMCID: PMC3132840

Abstract

Impaired regulation of renin in Dahl salt-sensitive rats (SS/JRHsdMcwi, SS) contributes to attenuated angiogenesis in this strain. This study examined angiogenic function and genomic structure of regions surrounding the renin gene using subcongenic strains of the SS and BN/NHsdMcwi (BN) rat to identify important genomic variations between SS and BN involved in angiogenesis. Three candidate regions on Chr 13 were studied: two congenic strains containing 0.89 and 2.62 Mb portions of BN Chr 13 that excluded the BN renin allele and a third strain that contained a 2.02 Mb overlapping region that included the BN renin allele. Angiogenesis induced by electrical stimulation of the tibialis anterior muscle was attenuated in the SS compared with the BN. Congenics carrying the SS renin allele had impaired angiogenesis, while strains carrying the BN renin allele had angiogenesis restored. The exception was a congenic including a region of BN genome 0.4 Mb distal to renin that restored both renin regulation and angiogenesis. This suggests that there is a distant regulatory element in the BN capable of restoring normal regulation of the SS renin allele. The importance of ANG II in the restored angiogenic response was demonstrated by blocking with losartan. Sequencing of the 4.05 Mb candidate region in SS and BN revealed a total of 8,850 SNPs and other sequence variants. An analysis of the genes and their variants in the region suggested a number of pathways that may explain the impaired regulation of renin and angiogenesis in the SS rat.

Author List

Stodola TJ, de Resende MM, Sarkis AB, Didier DN, Jacob HJ, Huebner N, Hummel O, Saar K, Moreno C, Greene AS

Author

Andrew S. Greene PhD Interim Vice Chair, Chief, Professor in the Biomedical Engineering department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Animals, Congenic
Body Weight
Chromosomes, Mammalian
Electric Stimulation
Exons
Gene Expression Regulation
Gene Regulatory Networks
Genome
Immunohistochemistry
Muscle, Skeletal
Neovascularization, Physiologic
Organ Size
RNA, Messenger
Rats
Rats, Inbred Dahl
Renin



View this publication's entry at the Pubmed website PMID: 21521778
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