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高血压同源近交系大鼠:它们在高血压基因搜寻中能有多大用处?

Congenic rats for hypertension: how useful are they for the hunting of hypertension genes?

作者信息

Nabika T, Kobayashi Y, Yamori Y

机构信息

Department of Laboratory Medicine, Shimane Medical University, Izumo, Japan.

出版信息

Clin Exp Pharmacol Physiol. 2000 Apr;27(4):251-6. doi: 10.1046/j.1440-1681.2000.03242.x.

Abstract
  1. Linkage studies have revealed quantitative trait loci (QTL) for blood pressure in the rat genome using genetic hypertensive rat models. To identify the genes responsible for hypertension, the construction of congenic rats is essential. 2. To date, several congenic strains have been obtained from spontaneously hypertensive or Dahl salt-sensitive rats. The results of these studies should be interpreted according to whether the rats carry the whole QTL region or not. 3. After establishing congenic strains, three strategies are possible: (i) an orthodox positional cloning in which, using subcongenic strains, the QTL region is cut down to smaller fragments suitable for physical mapping; (ii) a positional candidate strategy in which candidate genes in the QTL regions are studied; or (iii) physiological studies in which intermediate phenotypes directly associated with the hypertension gene are explored. Several other experimental strategies are also available using congenic strains as new animal models for hypertension. 4. To make the most of advances in DNA technology, the precise evaluation of the phenotypic difference between congenic strains carrying different QTL or between a congenic and parental strain is critical.
摘要
  1. 连锁研究已利用遗传性高血压大鼠模型在大鼠基因组中揭示了血压的数量性状基因座(QTL)。为了鉴定导致高血压的基因,构建近交系大鼠至关重要。2. 迄今为止,已从自发性高血压大鼠或 Dahl 盐敏感大鼠中获得了几种近交系。这些研究结果应根据大鼠是否携带整个 QTL 区域来解释。3. 在建立近交系后,有三种策略可行:(i)传统的定位克隆,即使用亚近交系将 QTL 区域缩小为适合物理图谱构建的较小片段;(ii)定位候选策略,即研究 QTL 区域中的候选基因;或(iii)生理学研究,即探索与高血压基因直接相关的中间表型。利用近交系作为高血压新动物模型还有其他几种实验策略。4. 为充分利用 DNA 技术的进展,精确评估携带不同 QTL 的近交系之间或近交系与亲本系之间的表型差异至关重要。

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