Hsgcq^{129S6/SvEvTac}
QTL Variant Detail

Summary

• QTL variant: Hsgcq^{129S6/SvEvTac}
• Name: hypertension soluble guanylate cyclase QTL; 129S6/SvEvTac
• MGI ID: MGI:5792155
• QTL: Hsgcq Location: unknown Genetic Position: Chr1, Syntenic

Variant origin

• Strain of Specimen: 129S6/SvEvTac

Variant description

• Allele Type: QTL
• Inheritance: Not Specified

Notes

Mapping and Phenotype information for this QTL, its variants and associated markers

J:188294

Male mice deficient in a nitric oxide receptor component, the alpha-1 subunit of soluble guanylate cyclase (sGC-alpha-1), are prone to hypertension in some, but not all, mouse strains. In the current study, the authors tested the hypothesis that differences in vascular reactivity between 129-Gucy1a3^tm1.1Brou mice on the C57BL/6J and 129S6/SvEvTac backgrounds contribute to the observed strain-related difference in blood pressure. A series of mapping studies identified, confirmed, then refined a locus significant for blood pressure on Chromosome 1 called Hsgcq (hypertension soluble guanylate cyclase QTL). All coordinates are reported relative to mm9 NCBI Build 37.

Genetic mapping was completed in a mapping population of reciprocal F1 crosses of 129-Gucy1a3^tm1.1Brou and B6.129-Gucy1a3^tm1.1Brou mice, whose F1 progeny were then intercrossed to yield F2 populations.

First, a linkage analysis in a first cohort of 92 F2 mice, using 120 genome-wide SNPs, identified a QTL on Chromosome 1 that influences blood pressure with a LOD score of 3.0.

Genotyping of a second independent cohort of 96 additional F2 mice yielded a collective LOD score of 5.3 at the chromosome 1 locus.

To refine the linkage peak through additional recombinants and higher marker density, the original 188 mice and a third independent cohort of 96 F2 mice (284 male mice total) were genotyped for 28 SNPs across the QTL on chromosome 1. Linkage at this locus was highly significant, with a final LOD score of 6.3 at SNP Mm37-1-130689858. This locus is designated Hsgcq. Hsgcq on Chromosome 1 covers approximately 40 Mb and is associated with hypertension (mean arterial pressure) in 129-Gucy1a3^tm1.1Brou.

Renin is the primary candidate gene for the Hsgcq locus. Renin is a key enzyme in the renin-angiotensin-aldosterone system that is responsible for the control of fluid homeostasis and blood pressure. Human and rat genomes contain a single gene for Renin. Mice, however, display two alternative genotypes at the Renin locus, with some inbred mouse strains (e.g., C57BL/6J) having only a single Renin gene designated Renin 1c, while others (e.g., 129S6/SvEvTac) possess two closely linked Renin genes on Chromosome 1 termed Renin 1d and Renin 2.

References

• Original: J:188294 Buys ES, et al., Genetic modifiers of hypertension in soluble guanylate cyclase alpha1-deficient mice. J Clin Invest. 2012 Jun 1;122(6):2316-25
• All: 1 reference(s)