A loss of genome buffering capacity of Dahl salt-sensitive model to modulate blood pressure as a cause of hypertension.
Essential hypertension is a complex trait influenced by multiple genes known as quantitative trait loci (QTLs) for blood pressure (BP). It is not clear, however, what roles these QTLs play in maintaining normotension. Insights gained toward the maintenance of normotension will shed light on how hypertension can result from a deficiency or malfunctioning of this maintenance. Currently, congenic strains were systematically constructed using Dahl salt-sensitive (DSS) and Lewis (LEW) rats not only to define QTLs (i.e. in DSS background), but also to ascertain effects of the same QTLs in preserving normotension (i.e. in LEW background), a first such study. Results showed that although LEW alleles for two QTLs on Chromosome (Chr) 18 lowered BP on the DSS background, their BP-increasing DSS alleles failed to influence BP in the LEW background. To further prove that the LEW background is resistant and the DSS background is susceptible to the effects of QTLs, BP-increasing alleles of a QTL on Chr 2 were introgressed into the DSS background, and its BP-decreasing alleles into the LEW background. Indeed, there was no BP-decreasing effect on the LEW background while demonstrating a BP-increasing effect on the DSS background. Thus, a genetic regulation of BP QTLs in the LEW genome inhibits BP changes by nullifying the effects of BP-altering QTLs. In comparison, the DSS genome must have lost the buffering capacity for stabilizing BP. The current work presents good evidence that a lack of regulation for functions of BP QTLs is a potential underlying cause of hypertension.
Charron
Sophie
S
Research Centre-CHUM, Montréal, Québec, Canada.
Lambert
Raphaëlle
R
Eliopoulos
Vasiliki
V
Duong
Chenda
C
Ménard
Annie
A
Roy
Julie
J
Deng
Alan Y
AY
D000818:Animals; D020296:Animals, Congenic; D001794:Blood Pressure / Q000235:genetics*; D002875:Chromosomes; D005260:Female; D016678:Genome; D006973:Hypertension / Q000235:genetics*; D008297:Male; D040641:Quantitative Trait Loci; D051381:Rats; D020303:Rats, Inbred Dahl / Q000235:genetics*; D011917:Rats, Inbred Lew; D012016:Reference Values