ArticleHypertension (Dallas, Tex. : 1979)2014
Refined mapping of a hypertension susceptibility locus on rat chromosome 12.
Article in Hypertension (Dallas, Tex. : 1979), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 10 citations in OpenAlex.
- Article
- Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes.Journal of biomedical science · 2020Review
- Association of ECE1 gene polymorphisms and essential hypertension risk in the Northern Han Chinese: A case-control study.Molecular genetics & genomic medicine · 2020Article
- Mapping genetic modifiers of radiation-induced cardiotoxicity to rat chromosome 3.American journal of physiology. Heart and circulatory physiology · 2019Article
- Dr Lewis Kitchener Dahl, the Dahl rats, and the "inconvenient truth" about the genetics of hypertension.Hypertension (Dallas, Tex. : 1979) · 2015Article
- Vascular dysfunction precedes hypertension associated with a blood pressure locus on rat chromosome 12.American journal of physiology. Heart and circulatory physiology · 2014Article
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9 authors at 1 institution in 1 country.
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Abstract
Previously, we found that transferring 6.1 Mb of salt-sensitive (SS) chromosome 12 (13.4-19.5 Mb) onto the consomic SS-12(BN) background significantly elevated mean arterial pressure in response to an 8% NaCl diet (178±7 versus 144±2 mm Hg; P<0.001). Using congenic mapping, we have now narrowed the blood pressure locus by 86% from a 6.1-Mb region containing 133 genes to an 830-kb region (chr12:14.36-15.19 Mb) with 14 genes. Compared with the SS-12(BN) consomic, the 830-kb blood pressure locus was associated with a ∆+15 mm Hg (P<0.01) increase in blood pressure, which coincided with elevated albuminuria (∆+32 mg/d; P<0.001), proteinuria (∆+48 mg/d; P<0.01), protein casting (∆+154%; P<0.05), and renal fibrosis (∆+79%; P<0.05). Of the 14 genes residing in the 830-kb locus, 8 were differentially expressed, and among these, Chst12 (carbohydrate chondroitin 4 sulfotransferase 12) was most consistently downregulated by 2.6- to 4.5-fold (P<0.05) in both the renal medulla and cortex under normotensive and hypertensive conditions. Moreover, whole genome sequence analysis of overlapping blood pressure loci revealed an ≈86-kb region (chr12:14 541 567-14 627 442 bp) containing single-nucleotide variants near Chst12 that are unique to the hypertensive SS strain when compared with the normotensive Brown Norway, Dahl salt-resistant, and Wistar-Kyoto strains. Finally, the 830-kb interval is syntenic to a region on human chromosome 7 that has been genetically linked to blood pressure, suggesting that insight gained from our SS-12(BN) congenic strain may be translated to a better understanding of human hypertension.
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