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

Genetic contamination of Dahl SS/Jr rats. Impact on studies of salt-sensitive hypertension.
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Dahl SS/Jr 大鼠的基因污染。

DOI:
10.1161/01.hyp.23.6.786
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发表时间:
1994
期刊:
Hypertension (Dallas, Tex. : 1979)
影响因子:
--
通讯作者:
MorrisJr,RC
MorrisJr,RC
中科院分区:
--
文献类型:
--
作者:
StLezin,EM;Pravenec,M;Wong,A;Wang,JM;Merriouns,T;Newton,S;Stec,DE;Roman,RJ;Lau,D;MorrisJr,RC

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Dahl 盐敏感大鼠(SS/Jr)是广泛使用的盐敏感高血压动物模型。 SS/Jr 大鼠被认为是高度近交系,并且对氯化钠的致高血压作用一致敏感,但我们最近观察到来自 Harlan Sprague Dawley, Inc. 的 SS/Jr 大鼠对补充膳食盐的血压反应表现出相当大的变异性。为了测试市售 SS/Jr 大鼠是否受到基因污染,因此不再完全近交,我们对从 Harlan Sprague Dawley 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个不同染色体上的基因座的杂合性和/或非典型等位基因变异的分子证据。许多大鼠也未能表现出对盐敏感的血压表型。我们得出的结论是,美国唯一一家 Dahl 大鼠销售的 SS/Jr 大鼠受到基因污染,并且对盐的致高血压作用具有抵抗力。这些发现对如何解释从 Harlan Sprague Dawley 获得的 SS/Jr 大鼠进行的研究提出了严重质疑。
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.