1. Physiol Genomics. 2009 Mar 3;37(1):52-7. doi: 10.1152/physiolgenomics.90299.2008.
Epub 2009 Jan 6.
Congenic strains provide evidence that four mapped loci in chromosomes 2, 4, and
16 influence hypertension in the SHR.
Aneas I(1), Rodrigues MV, Pauletti BA, Silva GJ, Carmona R, Cardoso L, Kwitek AE,
Jacob HJ, Soler JM, Krieger JE.
Author information:
(1)Heart Institute (InCor), University of São Paulo Medical School, São Paulo,
SP, Brazil.
To dissect the genetic architecture controlling blood pressure (BP) regulation in
the spontaneously hypertensive rat (SHR) we derived congenic rat strains for four
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 or 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. On high
salt intake (1% NaCl in drinking water for 2 wk), 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 four QTLs
affected BP phenotypes differently: 1) in the presence of high salt intake
(chromosome 16), 2) only associated with normal salt intake (chromosome 4), and
3) regardless of salt intake (chromosome 2c and 2a). Moreover, salt sensitivity
was abrogated in congenics SHR.BN2a and SHR.BN16. Finally, we provide evidence
for the influence of genetic background on 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 four mapped BP QTLs
in the SHR under basal and/or salt loading conditions unforeseen by the analysis
of the F2 cross.
PMID: 19126752 [PubMed - indexed for MEDLINE]
PUBMED: 19126752
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