RGD Reference Report - Congenic strains provide evidence that four mapped loci in chromosomes 2, 4, and 16 influence hypertension in the SHR. - Rat Genome Database

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

Authors: Aneas, I  Rodrigues, MV  Pauletti, BA  Silva, GJ  Carmona, R  Cardoso, L  Kwitek, AE  Jacob, HJ  Soler, JM  Krieger, JE 
Citation: Aneas I, etal., Physiol Genomics. 2009 Mar 3;37(1):52-7. Epub 2009 Jan 6.
RGD ID: 2306880
Pubmed: (View Article at PubMed) PMID:19126752
DOI: Full-text: DOI:10.1152/physiolgenomics.90299.2008

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.

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Objects Annotated

QTLs
Bp336  (Blood pressure QTL 336)
Bp337  (Blood pressure QTL 337)
Bp338  (Blood pressure QTL 338)
Bp339  (Blood pressure QTL 339)

Objects referenced in this article
QTL Bp18 Blood pressure QTL 18 Rattus norvegicus
QTL Bp19 Blood pressure QTL 19 Rattus norvegicus
QTL Bp21 Blood pressure QTL 21 Rattus norvegicus
QTL Bp23 Blood pressure QTL 23 Rattus norvegicus

Additional Information