1. Hypertension. 1998 Oct;32(4):639-46.
Successful isolation of a rat chromosome 1 blood pressure quantitative trait
locus in reciprocal congenic strains.
Frantz SA(1), Kaiser M, Gardiner SM, Gauguier D, Vincent M, Thompson JR, Bennett
T, Samani NJ.
Author information:
(1)Departments of Cardiology and Ophthalmology, University of Leicester,
Leicester, UK.
Comment in
Hypertension. 1998 Oct;32(4):647-8.
Linkage analyses in experimental crosses of hypertensive and normotensive rats
have strongly suggested the presence of a quantitative trait locus (QTL)
influencing blood pressure on rat chromosome 1, at or near the Sa gene. To
confirm the presence of such a locus and move toward identification of the
causative gene, we have developed, through targeted breeding over 10 generations
using an Sa gene polymorphism to select breeders at each generation, 2 congenic
strains, 1 containing a segment of spontaneously hypertensive rat (SHR)
chromosome 1 in a Wistar-Kyoto rat (WKY) genetic background (WKY.SHR-Sa), and the
other a segment of WKY chromosome 1 in an SHR background (SHR.WKY-Sa). WKY.SHR-Sa
contains at least approximately 26 cM of SHR chromosome 1, between markers
mD7mit206 and D1Mit2 (and including the SHR allele of the Sa gene), and
SHR.WKY-Sa carries at least approximately 15 cM of WKY chromosome 1, between
mD7mit206 and D1Wox34 (and including the WKY allele of the Sa gene). Blood
pressure of WKY.SHR-Sa rats measured at 16, 20, and 25 weeks of age was
significantly higher than that of WKY, whereas blood pressure of SHR.WKY-Sa rats
was significantly lower than that of SHR. At 25 weeks, the mean differences in
systolic and diastolic blood pressure between WKY.SHR-Sa and WKY were +11.5 mm Hg
(P=0.001) and +11.6 mm Hg mm Hg (P<0.001), respectively. The corresponding
differences between SHR.WKy-Sa and SHR were -11.3 mm Hg (P=0.002) and -9.1 mm Hg
(P=0.005), respectively. The differences represent about one fifth of the blood
pressure difference between SHR and WKY. Renal Sa mRNA levels in the congenic
strains reflected their Sa allele with a high level in WKY. SHR-Sa and a low
level in SHR.WKY-Sa, consistent with previous data suggesting that the level of
Sa expression is primarily determined by cis-acting elements in or near the Sa
gene. Our results show that we have successfully isolated a major rat chromosome
1 blood pressure QTL located in the vicinity of the Sa gene in reciprocal
congenic strains derived from SHR and WKY. The strains can now be used to further
define the region containing the QTL and also to characterize intermediary
mechanisms through which the QTL influences blood pressure. In addition,
comparison of the regions introgressed in our congenic strains with the location
of the peak LOD score for chromosome 1 blood pressure QTL in second filial
generation progeny derived from our SHRxWKY cross suggests that there may be at
least 1 further QTL influencing blood pressure on this rat chromosome.
PMID: 9774356 [PubMed - indexed for MEDLINE]
PUBMED: 9774356
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