Toland Edward J, Yerga-Woolwine Shane, Farms Phyllis, Cicila George T, Saad Yasser, Joe Bina
Physiological Genomics Laboratory, Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH 43614-5804, USA.
J Hypertens. 2008 Nov;26(11):2134-41. doi: 10.1097/HJH.0b013e32830ef95c.
A blood pressure (BP) quantitative trait locus (QTL) was previously located within 117 kb on rat chromosome 9 (RNO9) using hypertensive Dahl salt-sensitive and normotensive Dahl salt-resistant rats. An independent study between two hypertensive rat strains, the Dahl salt-sensitive rat and the spontaneously hypertensive rat (SHR), also detected a QTL encompassing this 117 kb region. Dahl salt-sensitive alleles in both of these studies were associated with increased BP. To map SHR alleles that decrease BP in the Dahl salt-sensitive rat, a panel of eight congenic strains introgressing SHR alleles onto the Dahl salt-sensitive genetic background were constructed and characterized. S.SHR(9)x3B, S.SHR(9)x3A and S.SHR(9)x2B, the congenic regions of which span a portion or all of the 1 logarithm of odds (LOD) interval identified by linkage analysis, did not significantly alter BP. However, S.SHR(9), S.SHR(9)x4A, S.SHR(9)x7A, S.SHR(9)x8A and S.SHR(9)x10A, the introgressed segments of which extend distal to the 1 LOD interval, significantly reduced BP. The shortest genomic segment, BP QTL1, to which this BP-lowering effect can be traced is the differential segment of S.SHR(9)x4A and S.SHR(9)x2B, to which an urinary protein excretion QTL also maps. However, the introgressed segment of S.SHR(9)x10A, located outside of this QTL1 region, represented a second BP QTL (BP QTL2) having no detectable effects on urinary protein excretion. In summary, the data suggest that there are multiple RNO9 alleles of the SHR that lower BP of the Dahl salt-sensitive rat with or without detectable effects on urinary protein excretion and that only one of these BP QTLs, QTL1, overlaps with the 117 kb BP QTL region identified using Dahl salt-sensitive and Dahl salt-resistant rats.
先前利用高血压性达氏盐敏感大鼠和正常血压性达氏盐抵抗大鼠，在大鼠9号染色体（RNO9）上117 kb范围内定位了一个血压（BP）数量性状基因座（QTL）。在两种高血压大鼠品系——达氏盐敏感大鼠和自发性高血压大鼠（SHR）之间开展的一项独立研究，也检测到一个包含该117 kb区域的QTL。这两项研究中的达氏盐敏感等位基因均与血压升高相关。为了在达氏盐敏感大鼠中定位降低血压的SHR等位基因，构建并鉴定了一组8个近交系，即将SHR等位基因渗入到达氏盐敏感遗传背景中。S.SHR(9)x3B、S.SHR(9)x3A和S.SHR(9)x2B，其近交区域跨越连锁分析确定的1个优势对数（LOD）区间的一部分或全部，并未显著改变血压。然而，S.SHR(9)、S.SHR(9)x4A、S.SHR(9)x7A、S.SHR(9)x8A和S.SHR(9)x10A，其渗入片段延伸至1 LOD区间的远端，显著降低了血压。能够追溯到这种降血压效应的最短基因组片段BP QTL1，是S.SHR(9)x4A和S.SHR(9)x2B的差异片段，一个尿蛋白排泄QTL也定位于此。然而，位于该QTL1区域之外的S.SHR(9)x10A的渗入片段，代表了第二个对尿蛋白排泄无可检测影响的血压QTL（BP QTL2）。总之，数据表明SHR存在多个RNO9等位基因，这些等位基因可降低达氏盐敏感大鼠的血压，对尿蛋白排泄有或无可检测影响，并且这些血压QTL中只有一个，即QTL1，与利用达氏盐敏感和达氏盐抵抗大鼠鉴定出的117 kb血压QTL区域重叠。
