Sequence analysis of the alpha 1 Na+,K(+)-ATPase gene in the Dahl salt-sensitive rat.
Sequence analysis of the alpha 1 Na+,K(+)-ATPase gene in the Dahl salt-sensitive rat.
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Dahl 盐敏感大鼠α1 Na ,K( )-ATPase 基因的序列分析。
DOI：
10.1161/01.hyp.18.5.689
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Kurtz,TW
中科院分区：
文献类型：
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作者：
Simonet,L;StLezin,E;Kurtz,TW
在近交系Dahl盐敏感大鼠（SS/Jr品系）中，Na+，K（+）-ATP酶α 1亚基亚型276位氨基酸的DNA编码序列中的T对A的颠换可能损害离子转运并参与高血压的发病。这一假说具有重大的科学意义，因为它代表了第一次尝试在DNA水平上明确定义突变的基础上解释盐敏感性高血压的发病机制。我们设计了一种聚合酶链反应技术来筛选多个SS/Jr大鼠基因组DNA中编码Na+，K（+）-ATP酶α 1亚基的互补DNA（cDNA）中的T为A颠换。当8只来自哈兰斯普拉格道利公司的Dahl SS/Jr大鼠。用聚合酶链反应技术检测，我们没有发现Na+，K（+）-ATP酶基因突变的证据。在三个SS/Jr大鼠的基因的直接序列分析也没有显示T为A颠换。这些结果1）有力地表明，市售Dahl SS/Jr大鼠在Na+，K（+）-ATP酶α 1亚基同种型中编码氨基酸276的基因组DNA序列中不携带T对A的颠换，2）提出了先前在SS/Jr大鼠cDNA中发现突变可能是由于cDNA合成期间逆转录酶错误所致的可能性。
In the inbred Dahl salt-sensitive rat (SS/Jr strain), it has been proposed that a T for A transversion in the DNA sequence encoding amino acid 276 in the alpha 1 subunit isoform of Na+,K(+)-ATPase may impair ion transport and contribute to the pathogenesis of hypertension. This hypothesis is of major scientific interest because it represents the first attempt to explain the pathogenesis of salt-sensitive hypertension on the basis of a specifically defined mutation at the DNA level. We devised a polymerase chain reaction technique to screen the genomic DNA of multiple SS/Jr rats for the T for A transversion reported in the complementary DNA (cDNA) encoding the alpha 1 subunit of Na+,K(+)-ATPase. When eight Dahl SS/Jr rats from Harlan Sprague Dawley Inc. were tested with the polymerase chain reaction technique, we found no evidence of this mutation in the Na+,K(+)-ATPase gene. Direct sequence analysis of the gene in three SS/Jr rats also did not show the T for A transversion. These results 1) strongly suggest that commercially available Dahl SS/Jr rats do not carry a T for A transversion in the genomic DNA sequence encoding amino acid 276 in the alpha 1 subunit isoform of Na+,K(+)-ATPase and 2) raise the possibility that the previous finding of a mutation in the cDNA of the SS/Jr rat may have been due to a reverse transcriptase error during cDNA synthesis.