The α1 Na,K-ATPase gene is a susceptibility hypertension gene in the Dahl salt-sensitiveHSD rat
The α1 Na,K-ATPase gene is a susceptibility hypertension gene in the Dahl salt-sensitiveHSD rat
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DOI：
10.1172/jci3868
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发表时间：
1998-09-15
影响因子：
15.9
通讯作者：
Ruiz-Opazo, N
中科院分区：
文献类型：
--
作者：
Herrera, VLM;Xie, HX;Ruiz-Opazo, N
尽管原发性高血压很普遍，但由于其决定因素的复杂性，其潜在的遗传基础尚未阐明。为了鉴定高血压易感基因，我们采用了一种整合分子、转基因和遗传分析的方法，使用 Dahl 盐敏感 (S) 和 Dahl 盐抗性 (R) 大鼠来确定基因型和表型。为了确定 Dahl S Q276L α 1 Na,K-ATPase 基因变体的作用，我们开发了转基因 Dahl S 大鼠，其带有由同源 wt 启动子区域 Tg[wt α 1] 指导的 Dahl R 野生型 (wt) 油 Na,K-ATPase cDNA。与非转基因 Dahl S 对照相比，转基因 Dahl S 大鼠表现出较少的盐敏感性高血压、较少的高血压肾病和较长的寿命。 F2(SXR) 雄性大鼠的总染色体 2 连锁分析检测到 cll Na,K-ATPase 位点与盐敏感性高血压的共分离。这些数据支持α1 Na,K-ATPase基因作为Dahl S大鼠模型中盐敏感性高血压的易感基因，并为人类高血压中α1 Na,K-ATPase位点的研究提供基础。
Despite the prevalence of essential hypertension, its underlying genetic basis has not been elucidated due to the complexities of its determinants. To identify a hypertension susceptibility gene, we used an approach that integrates molecular, transgenic, and genetic analysis using Dahl salt-sensitive (S) and Dahl salt-resistant (R) rats ascertained for genotype and phenotype. To determine the role of the Dahl S Q276L alpha 1 Na,K-ATPase gene variant, we developed transgenic Dahl S rats bearing the Dahl R wild-type (wt) oil Na,K-ATPase cDNA directed by the cognate wt promoter region, Tg[wt alpha 1]. Transgenic Dahl S rats exhibited less salt-sensitive hypertension, less hypertensive renal disease, and longer life span when compared with non-transgenic Dahl S controls. Total chromosome 2 linkage analysis of F2(SXR) male rats detects cosegregation of the cll Na,K-ATPase locus with salt-sensitive hypertension. These data support the alpha 1 Na,K-ATPase gene as a susceptibility gene for salt-sensitive hypertension in the Dahl S rat model, and provide the basis for the study of the alpha 1 Na,K-ATPase locus in human hypertension.