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达尔SS/Jr大鼠的基因污染。对盐敏感性高血压研究的影响。

Genetic contamination of Dahl SS/Jr rats. Impact on studies of salt-sensitive hypertension.

作者信息

St Lezin E M, Pravenec M, Wong A, Wang J M, Merriouns T, Newton S, Stec D E, Roman R J, Lau D, Morris R C

机构信息

Department of Laboratory Medicine, University of California, San Francisco.

出版信息

Hypertension. 1994 Jun;23(6 Pt 1):786-90. doi: 10.1161/01.hyp.23.6.786.

DOI:10.1161/01.hyp.23.6.786
PMID:8206578
Abstract

The Dahl salt-sensitive rat (SS/Jr) is a widely used animal model of salt-sensitive hypertension. SS/Jr rats are believed to be highly inbred and uniformly sensitive to the hypertensinogenic effects of sodium chloride, but we have recently observed that SS/Jr rats from Harlan Sprague Dawley, Inc, exhibit considerable variability in their blood pressure response to supplemental dietary salt. To test the possibility that commercially available SS/Jr rats are genetically contaminated and therefore no longer fully inbred, we performed molecular genetic studies and blood pressure measurements in several groups of SS/Jr rats purchased from Harlan Sprague Dawley. We found molecular evidence of heterozygosity and/or atypical allelic variants involving loci on at least five different chromosomes. Many of the rats also failed to exhibit a salt-sensitive blood pressure phenotype. We conclude that SS/Jr rats being sold by the only commercial vendor of Dahl rats in the United States are genetically contaminated and resistant to the hypertensinogenic effects of salt. These findings raise serious questions about the interpretation of research conducted with SS/Jr rats obtained from Harlan Sprague Dawley.

摘要

达尔盐敏感大鼠(SS/Jr)是一种广泛应用的盐敏感性高血压动物模型。人们认为SS/Jr大鼠高度近亲繁殖,且对氯化钠的致高血压作用具有一致的敏感性,但我们最近观察到,购自哈兰·斯普拉格·道利公司的SS/Jr大鼠在对补充膳食盐的血压反应上表现出相当大的变异性。为了检验市售SS/Jr大鼠受到基因污染因而不再完全近亲繁殖的可能性,我们对从哈兰·斯普拉格·道利公司购买的几组SS/Jr大鼠进行了分子遗传学研究和血压测量。我们发现了涉及至少五条不同染色体上基因座的杂合性和/或非典型等位基因变异的分子证据。许多大鼠也未表现出盐敏感性血压表型。我们得出结论,美国达尔大鼠唯一的商业供应商所售的SS/Jr大鼠受到了基因污染,并且对盐的致高血压作用具有抗性。这些发现对使用从哈兰·斯普拉格·道利公司获得的SS/Jr大鼠所开展研究的解读提出了严重质疑。

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Genetic contamination of Dahl SS/Jr rats. Impact on studies of salt-sensitive hypertension.达尔SS/Jr大鼠的基因污染。对盐敏感性高血压研究的影响。
Hypertension. 1994 Jun;23(6 Pt 1):786-90. doi: 10.1161/01.hyp.23.6.786.
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