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(Hypertension. 1999;33:261-265.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Role of Chromosome X in the Sabra Rat Model of Salt-Sensitive Hypertension

Chana Yagil; Marina Sapojnikov; Reinhold Kreutz; Heiko Zürcher; Detlev Ganten; Yoram Yagil

From the Laboratory for Molecular Medicine and Department of Nephrology and Hypertension (C.Y., M.S., Y.Y.), Faculty of Health Sciences, Ben-Gurion University, Barzilai Medical Center Campus, Ashkelon, Israel, and Benjamin Franklin Hospital (R.K., H.Z., D.G.), Free University of Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany.

Correspondence to Yoram Yagil, MD, Laboratory for Molecular Medicine, Department of Nephrology and Hypertension, Barzilai Medical Center, Ashkelon 78306, Israel. E-mail labmomed{at}bgumail.bgu.ac.il

Abstract—We carried out a total genome screen in the Sabra rat model of hypertension to detect salt-susceptibility genes. We previously reported in male animals the presence of 2 major quantitative trait loci (QTLs) on chromosome 1 that together accounted for most of the difference in the blood pressure (BP) response to salt loading between Sabra hypertension-prone rats (SBH/y) and Sabra hypertension-resistant rats (SBN/y). In females, we reported on 2 major QTLs on chromosomes 1 and 17 that together accounted for only two thirds of the difference in the BP response between the strains. On the basis of phenotypic patterns of inheritance in reciprocal F₂ crosses, we proposed a role of the X chromosome. We therefore continued the search for the missing QTL in females that would account for the remaining difference in the BP response between the 2 strains using newly developed microsatellite markers and focusing on chromosome X. We screened an F₂ cross, consisting of 371 females and 336 males, using 19 polymorphic chromosome X microsatellite markers. We analyzed the averages of BP by genotype using ANOVA and the individual data using MAPMAKER/QTL. In female F₂ progeny, we identified a segment on chromosome X that spans over 33.4 cM and shows significant cosegregation (P<0.001) of 14 microsatellite markers (demarcated by DXRat4 and DXMgh10) with systolic BP after salt loading. This segment has 2 apparent peaks at DXRat4 and DXRat13, with a BP effect of 14 mm Hg for each. Multipoint linkage analysis with a free model detected 3 peaks (logarithm of the odds ratio [LOD] score >4.3) within the same chromosomal segment: One between DXMgh9 and DXMit4 (LOD 4.9; 6.1% of variance), a second between DXMgh12 and DXRat8 (LOD 5.2; 7.2% of variance), and a third between DXRat2 and DXRat4 (LOD 5.8; 7.5% of variance). On the basis of these findings and until congenic strains become available, our working assumption is that within chromosome X, 1 to 3 genetic loci contribute importantly to the BP response of female Sabra rats to salt. In male F₂ progeny, we detected no significant cosegregation of any region on chromosome X with the BP response to salt loading. We conclude that in the female rat, salt susceptibility is mediated by 3 to 5 gene loci on chromosomes 1, 17, and X, whereas in the male rat, the X chromosome does not affect the BP response to salt.

Key Words: sodium • rats, Sabra • sex • genome • microsatellite • genes • linkage, genetic

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