Huang H, Pravenec M, Wang J M, Kren V, St Lezin E, Szpirer C, Szpirer J, Kurtz T W
Department of Laboratory Medicine, University of California, San Francisco, USA.
J Hypertens. 1995 Nov;13(11):1247-51. doi: 10.1097/00004872-199511000-00005.
To investigate whether mutations in the beta subunit of the epithelial sodium channel (Scnn1b) contribute to the pathogenesis of hypertension in the spontaneously hypertensive rat (SHR) and the Dahl salt-sensitive rat.
We determined the chromosome location of the rat Scnn1b gene, tested for cosegregation with blood pressure, and sequenced near full-length Scnn1b complementary DNAs (cDNAs) from SHR and Dahl salt-sensitive rats.
Chromosome mapping was performed by somatic cell hybrid analysis and by linkage analysis in recombinant inbred strains derived from SHR and Brown-Norway rats. Cosegregation analysis was performed by testing for correlations between blood pressure and Scnn1b genotypes in these strains. DNA sequencing was performed on cDNAs prepared from reverse-transcribed messenger RNA derived from rat kidney.
The Scnn1b gene was closely linked to the Sa gene on rat chromosome 1. Blood pressure correlated significantly with Scnn1b gene in the recombinant inbred strains. Analysis of near full-length Scnn1b cDNAs from SHR and Dahl rats failed to reveal any coding sequence mutations that could affect the predicted amino acid sequence of the Scnn1b protein.
The Scnn1b gene maps near the Sa gene in a region of rat chromosome 1 involved in the inherited control of blood pressure. If disordered activity of the epithelial cell sodium channel contributes to the pathogenesis of hypertension in the SHR or Dahl models, it must stem from genetic lesions in sequences that regulate Scnn1b function or in sequences important to the structure or function of the other sodium channel subunits.
研究上皮钠通道（Scnn1b）β亚基的突变是否导致自发性高血压大鼠（SHR）和 Dahl 盐敏感大鼠的高血压发病机制。
我们确定了大鼠 Scnn1b 基因的染色体定位，测试其与血压的共分离情况，并对来自 SHR 和 Dahl 盐敏感大鼠的近全长 Scnn1b 互补 DNA（cDNA）进行测序。
通过体细胞杂交分析和在源自 SHR 和 Brown-Norway 大鼠的重组近交系中进行连锁分析来进行染色体定位。通过测试这些品系中血压与 Scnn1b 基因型之间的相关性来进行共分离分析。对从大鼠肾脏逆转录的信使核糖核酸制备的 cDNA 进行 DNA 测序。
Scnn1b 基因与大鼠 1 号染色体上的 Sa 基因紧密连锁。在重组近交系中，血压与 Scnn1b 基因显著相关。对来自 SHR 和 Dahl 大鼠的近全长 Scnn1b cDNA 的分析未能揭示任何可能影响 Scnn1b 蛋白预测氨基酸序列的编码序列突变。
Scnn1b 基因定位于大鼠 1 号染色体上与血压遗传控制有关的区域中靠近 Sa 基因的位置。如果上皮细胞钠通道的紊乱活动导致 SHR 或 Dahl 模型中的高血压发病机制，那么它必定源于调节 Scnn1b 功能的序列或对其他钠通道亚基的结构或功能重要的序列中的遗传损伤。
