Physiol. Genomics AJP: Cell Physiology
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Physiol. Genomics (January 6, 2009). doi:10.1152/physiolgenomics.90299.2008
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Submitted on August 2, 2008
Revised on December 17, 2008
Accepted on December 17, 2008

Congenic strains provide evidence that four mapped loci in chromosomes 2, 4, and 16 influence hypertension in the SHR

Ivy Aneas1, Mariliza Volho Rodrigues2, Bianca A Pauletti2, Gustavo J. J. Silva2, Renata Carmona2, Leandro Cardoso2, Anne E Kwitek3, Howard J Jacob3, Julia M. P Soler4, and Jose E. Krieger2*

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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