Role of chromosome X in the Sabra rat model of salt-sensitive hypertension

We carried out a total genome screen in the Sabra rat model of hypertension to detect salt-susceptibility genes. We previously reported in male animal s the presence of 2 major quantitative trait loci (QTLs) on chromosome 1 th at together accounted for most of the difference in the blood pressure (BP) response to salt loading between Sabra hypertension-prone rats (SBH/y) and Sabre hypertension-resistant fats (SBN/y). In females, we reported on 2 ma jor QTLs on chromosomes 1 and 17 that together accounted for only two third s of the difference in the BP response between the strains. On the basis of phenotypic patterns of inheritance in reciprocal F-2 crosses, we proposed a role of the X chromosome. We therefore continued the search for the missi ng QTL in females that would account for the remaining difference in the BP response between the 2 strains using newly developed microsatellite marker s and focusing on chromosome X. We screened an F-2 cross, consisting of 371 females and 336 males, using 19 polymorphic chromosome X microsatellite ma rkers. We analyzed the averages of BP by genotype using ANOVA and the indiv idual data using MAPMAKER/QTL. In female F-2 progeny, we identified a segme nt on chromosome X that spans over 33.4 cM and shows significant cosegregat ion (P<0.001) of 14 microsatellite markers (demarcated by DXRat4 and DXMgh1 0) with systolic BP after salt loading. This segment has 2 apparent peaks a t DXRat4 and DXRat13, with a BP effect of 14 mm Hg for each. Multipoint lin kage analysis with a free model detected 3 peaks (logarithm of the odds rat io CLOD] score >4.3) within the same chromosomal segment: One between DXMgh 9 and DXMit4 (LOD 4.9; 6.1% of variance), a second between DXMgh12 and DXRa t8 (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 s trains become available, our working assumption is that within chromosome X , 1 to 3 genetic loci contribute importantly to the BP response of female S abra rats to salt. In male F-2 progeny, we detected no significant cosegreg ation of any region on chromosome X with the BP response to salt loading. W e 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 chr omosome does not affect the BP response to salt.