Genetic isolation of a quantitative trait locus on chromosome 18 associated with blood pressure and salt sensitivity in the SHR
Michal Pravenec
Abstract
Michal Pravenec
Abstract
Previous linkage studies in the spontaneously hypertensive rat (SHR) suggested a presence of a major quantitative trait locus (QTL) with effects on blood pressure and salt sensitivity on chromosome 18. To test this hypothesis, we developed an SHR.BN-chromosome 18 (SHR-18) congenic strain by transferring a segment of chromosome 18 between the Adrb2 and Ttr markers from the Brown Norway (BN/Cr) strain onto the SHR/Ola genetic background. The transfer of chromosome 18 segment resulted in a significant decrease in both systolic and diastolic blood pressures and a pronounced resistance to salt in SHR-18 congenic strain which contrasted to a significant increase in blood pressure in the SHR when rats were given 1% salt solution for drinking. After salt loading, the difference in systolic blood pressure achieved nearly 30 mm Hg. Blood pressure decrease in the SHR-18 congenic strain was accompanied by a significantly lower relative heart weights when compared to the SHR. These findings demonstrate that a QTL with major effects on blood pressure and salt sensitivity exists on a differential segment of chromosome 18 trapped within the new SHR congenic strain.
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Previous linkage studies in the spontaneously hypertensive rat (SHR) suggested a presence of a major quantitative trait locus (QTL) with effects on blood pressure and salt sensitivity on chromosome 18. To test this hypothesis, we developed an SHR.BN-chromosome 18 (SHR-18) congenic strain by transferring a segment of chromosome 18 between the Adrb2 and Ttr markers from the Brown Norway (BN/Cr) strain onto the SHR/Ola genetic background. The transfer of chromosome 18 segment resulted in a significant decrease in both systolic and diastolic blood pressures and a pronounced resistance to salt in SHR-18 congenic strain which contrasted to a significant increase in blood pressure in the SHR when rats were given 1% salt solution for drinking. After salt loading, the difference in systolic blood pressure achieved nearly 30 mm Hg. Blood pressure decrease in the SHR-18 congenic strain was accompanied by a significantly lower relative heart weights when compared to the SHR. These findings demonstrate that a QTL with major effects on blood pressure and salt sensitivity exists on a differential segment of chromosome 18 trapped within the new SHR congenic strain.
Key concepts: Congenic, Quantitative trait locus, Blood pressure, Locus (genetics), Chromosome, Chromosome 4, Chromosome 9, Internal medicine