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1 University of Sao Paulo
2 Heart Institute (InCor)/Univ Sao Paulo Med Sch
3 Medical College of Wisconsin
4 Inst Math & Stat/Univ Sao Paulo
* To whom correspondence should be addressed. E-mail: krieger{at}incor.usp.br.
To dissect the genetic architecture controlling blood pressure (BP) regulation in the Spontaneously Hypertensive Rat (SHR) we derived congenic rat strains for 4 previously mapped BP Quantitative Trait Loci (QTLs) in chromosomes 2, 4, and 16. Target chromosomal regions from the Brown Norway Rat (BN) averaging 13-29 cM were introgressed by marker-assisted breeding onto the SHR genome in 12-13 generations. Under normal salt-intake, QTLs on chromosomes 2a, 2c, and 4 were associated with significant changes in systolic BP (13, 20, and 15 mmHg, respectively), whereas the QTL on chromosome 16 had no measurable effect. Upon high salt intake (1% NaCl on drinking water for 2 weeks), the chromosome 16 QTL had a marked impact on SBP, as did the QTLs on chromosome 2a and 2c (18, 17 and 19 mmHg, respectively), but not the QTL on chromosome 4. Thus, these 4 QTLs affected BP phenotypes differently: 1) in the presence of high salt-intake (16), 2) only associated with normal salt-intake (4), and 3) regardless of salt-intake (2c and 2a). Moreover, salt-sensitivity was abrogated in congenics S.B2a and S.B16. Finally, we provide evidence for the influence of genetic background for the expression of the mapped QTLs individually or as a group. Collectively, these data reveal previously unsuspected nuances of the physiological roles of each of the 4 mapped BP QTLs in the SHR under basal and/or salt-loading condition unforeseen by the analysis of the F2 cross.
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