Rapp J P, Dene H, Deng A Y
Department of Physiology and Biophysics, Medical College of Ohio, Toledo 43699.
J Hypertens. 1994 Apr;12(4):349-55.
To survey inbred rat strains for renin alleles and to test those alleles for effects on blood pressure.
Rat strains with renin alleles different from the s allele carried by inbred Dahl salt-sensitive (SS/Jr) rats were crossed with SS/Jr rats and subsequently intercrossed to produce F2 populations. Thus, in each F2 population segregation of the s renin allele and a contrasting renin allele occurred. F2 rats were raised on a high-salt diet and their blood pressures were determined. The cosegregation of renin alleles with blood pressure was evaluated in each F2 population.
Renin alleles were recognized by the variable number of tandem repeats in the first intron of the renin gene and by a variable HindIII site in the fifth intron. Genotyping was by restriction fragment length polymorphism analysis.
Seven renin alleles were found, but breeding stock for only six of these alleles was available. From these stocks it was possible to construct five F2 populations in which the s renin allele segregated with a contrasting renin allele. In all five F2 populations the rats homozygous for the s allele had higher blood pressure than those homozygous for the contrasting renin allele, but statistical significance was most easily established in the F2 intercrossed offspring of an SS/Jr x inbred Dahl salt-resistant (SR/Jr) rat cross. This result was duplicated.
There are at least seven alleles in rats at the renin locus, allowing many pairwise allelic comparisons to be made. Of the five alleles compared with the s renin allele, the r allele of SR/Jr rats was unique in providing strong evidence for cosegregation with blood pressure. The naive expectation that all crosses should yield the same cosegregation result with blood pressure for a candidate locus is not consistent with either theory or the present experimental results.
调查近交系大鼠品系中的肾素等位基因，并测试这些等位基因对血压的影响。
将肾素等位基因与近交系达尔盐敏感（SS/Jr）大鼠携带的s等位基因不同的大鼠品系与SS/Jr大鼠杂交，随后进行互交以产生F2群体。因此，在每个F2群体中，s肾素等位基因和一个对比性肾素等位基因发生分离。F2大鼠采用高盐饮食饲养，并测定其血压。在每个F2群体中评估肾素等位基因与血压的共分离情况。
通过肾素基因第一个内含子中串联重复序列的可变数目以及第五个内含子中可变的HindIII位点来识别肾素等位基因。基因分型采用限制性片段长度多态性分析。
发现了7个肾素等位基因，但其中只有6个等位基因有繁殖种群。利用这些种群可以构建5个F2群体，其中s肾素等位基因与一个对比性肾素等位基因发生分离。在所有5个F2群体中，s等位基因纯合的大鼠血压高于对比性肾素等位基因纯合的大鼠，但在SS/Jr×近交系达尔盐抵抗（SR/Jr）大鼠杂交的F2互交后代中最容易确定统计学意义。这一结果得到了重复。
大鼠肾素基因座至少有7个等位基因，可进行许多成对的等位基因比较。在与s肾素等位基因比较的5个等位基因中，SR/Jr大鼠的r等位基因在提供与血压共分离的有力证据方面是独特的。对于候选基因座，所有杂交都应产生与血压相同的共分离结果这一单纯的预期与理论或当前实验结果均不一致。
