Genetically defined risk of salt sensitivity in an intercross of Brown Norway and Dahl S rats
Genetically defined risk of salt sensitivity in an intercross of Brown Norway and Dahl S rats
复制标题
DOI：
10.1152/physiolgenomics.2000.2.3.107
复制
发表时间：
2000-04-27
影响因子：
4.6
通讯作者：
Jacob, HJ
中科院分区：
文献类型：
--
作者：
Cowley, AW;Stoll, M;Jacob, HJ
进行遗传分离分析，以确定与反映盐敏感性的动脉血压特征协同分离的基因。由近交系SS/JrHsd/MCW(Dahl盐敏感)和BN/SSN/MCW(Brown挪威)大鼠杂交而成，共113只F2雄性大鼠。大鼠从9~13wk开始喂食8%的食盐，在高盐摄入的第4周，非麻醉大鼠用埋置动脉导管测量动脉血压。在高盐压力记录的第三天结束时，用LaSix和低钠(0.4%)饮食治疗1.5天后，测定动脉压对盐耗竭的反应。265个SSLP标记的全基因组扫描发现，代表盐敏感性的两个不同指数的7种动脉压表型在不同的时间和环境下被定位到大鼠18号染色体的同一区域。盐敏感性的性状受到18号染色体该区域SS等位基因存在的强烈影响，并且那些SS/SS纯合子大鼠在钠缺乏后平均动脉压的下降(29+/-2毫米汞)显著高于纯合子BN/BN(17+/-3毫米汞)或杂合子(22+/-2毫米汞)大鼠。大鼠18号染色体的这一区域对应于人类5号染色体的长臂和人类18号染色体的一个区域，该区域与人类高血压有关。考虑到这些不同的血压特征映射到同一区域的可能性不大，我们相信这些数据提供了证据，证明大鼠18号染色体的这个区域在盐诱导的高血压中发挥着重要作用。
A genetic segregation analysis was performed to identify genes that cosegregate with arterial blood pressure traits reflective of salt sensitivity. A population of 113 F2 male rats was derived from an intercross of inbred SS/JrHsd/Mcw (Dahl salt-sensitive) and BN/SsN/Mcw (Brown Norway) rats. Rats were maintained on an 8% salt diet from the age of 9 to 13 wk, and arterial pressure was measured for 3 h daily during the 4th wk of high salt intake in unanesthetized rats using implanted arterial catheters. At the end of the 3rd day of high-salt pressure recordings, the arterial pressure response to salt depletion was determined 1.5 days following treatment with Lasix and a low-sodium (0.4%) diet. A genome-wide scan using 265 polymorphic simple sequence length polymorphism (SSLP) markers found that seven arterial pressure phenotypes determined at different times and circumstances, and representing two distinct indexes of salt sensitivity, mapped to the same region of rat chromosome 18. The trait of salt sensitivity was strongly influenced by the presence of SS alleles in this region of chromosome 18, and those rats which were homozygote SS/SS exhibited a significantly greater reduction of mean arterial pressure following sodium depletion (29 +/- 2 mmHg) than homozygote BN/BN (17 +/- 3 mmHg) or heterozygotic (22 +/- 2 mmHg) rats. This region of rat chromosome 18 corresponds to the long arm of human chromosome 5 and a region of human chromosome 18 that has been linked to hypertension in humans. Given the unlikely chance of these different blood pressure traits mapping to the same region, we believe these data provide evidence that this region of rat chromosome 18 plays an important role in salt-induced hypertension.