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(Hypertension. 2000;35:225.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Genetic Analysis of Rat Chromosome 1 and the Sa Gene in Spontaneous Hypertension

Elizabeth St. Lezin; Weizhong Liu; Jia-Ming Wang; Ying Yang; Nianning Qi; Vladimir Kren; Vaclav Zidek; Theodore W. Kurtz; Michal Pravenec

From the Department of Laboratory Medicine (E.S., W.L., J.-M.W., Y.Y., N.Q., T.W.K.), University of California, San Francisco; Institute of Biology and Medical Genetics (V.K., M.P.), 1st Medical Faculty, Charles University, Prague, Czech Republic; and Institute of Physiology (V.K., M.P.) and Czech Academy of Sciences, Prague, Czech Republic.

Correspondence to Elizabeth St. Lezin, MD, Department of Laboratory Medicine, UCSF/Mt. Zion Medical Center, 1600 Divisadero St, San Francisco, CA 94143-1613. E-mail stlezin{at}pangloss.ucsf.edu

Abstract—Linkage studies in segregating populations derived from the spontaneously hypertensive rat (SHR) indicate that a blood pressure quantitative trait locus exists on rat chromosome 1 in the vicinity of the Sa gene. On the basis of these findings and the observation of increased renal expression of the Sa gene in SHR versus normotensive rats, the Sa gene has been proposed as a candidate gene for spontaneous hypertension. In SHR congenic strains, we and others have found that replacement of a segment of SHR chromosome 1 that contains the Sa gene with the corresponding chromosome segment from a normotensive Brown Norway (BN) rat or Wistar-Kyoto rat can reduce blood pressure. To test whether the Sa gene is necessary for the effect of this region of chromosome 1 on blood pressure, we studied a new SHR congenic subline that harbors a smaller segment of BN chromosome 1 that does not include the Sa gene. Transfer of this subregion of chromosome 1 from the BN rat onto the SHR background was associated with significant reductions in blood pressure comparable to those previously observed on transfer of a larger region of chromosome 1 that included the Sa gene. Thus, in the SHR-BN model of hypertension, the results of these mapping studies (1) demonstrate that molecular variation in the Sa gene is not required for the effect of this region of chromosome 1 on blood pressure and (2) should direct attention toward other candidate genes within the differential chromosome segment of the new congenic subline.

Key Words: hypertension, genetic • genes • rats, inbred SHR • rats, inbred WKY

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