Cicila G T, Rapp J P, Bloch K D, Kurtz T W, Pravenec M, Kren V, Hong C C, Quertermous T, Ng S C
Cosmopolitan International Diabetes Center, University of Missouri, Columbia 65212.
J Hypertens. 1994 Jun;12(6):643-51.
To determine whether the endothelin-1 or endothelin-3 genes are genetically linked with blood pressure and relative heart weight in segregating rat populations, in the context of an elevated dietary sodium chloride intake.
Endothelin-1 and endothelin-3 genotypes of rats in segregating populations, derived from crosses of Dahl salt-sensitive (SS/Jr) rats with contrasting inbred strains, including Lewis rats, spontaneously hypertensive rats and Dahl salt-resistant (SR/Jr) rats, were determined using restriction fragment length polymorphisms. Segregating populations were fed a high (8%)-sodium chloride diet. Linkage of genotype with blood pressure or relative heart weight was determined by analysis of variance. Chromosomal location of the rat endothelin-3 gene was determined by genotyping a panel of recombinant inbred strains.
Two alleles for the endothelin-1 gene and three alleles for the endothelin-3 gene were identified. The endothelin-1 locus did not cosegregate with blood pressure or relative heart weight. The endothelin-3 locus cosegregated with blood pressure and relative heart weight in an SS/Jr x F1 (SS/Jr x SR/Jr) population, but not in populations containing a higher percentage of genes from the SR/Jr strain. The endothelin-3 and seminal vesicle protein-1 loci were linked and located on rat chromosome 3.
The endothelin-3 gene is, or is linked to, a locus on chromosome 3 that regulates blood pressure and relative heart weight in inbred Dahl rats, and these effects were strongly dependent on the genetic background.
在高盐饮食摄入的情况下，确定内皮素-1或内皮素-3基因在分离的大鼠群体中是否与血压和相对心脏重量存在遗传连锁关系。
利用限制性片段长度多态性确定来自Dahl盐敏感（SS/Jr）大鼠与包括Lewis大鼠、自发性高血压大鼠和Dahl盐抵抗（SR/Jr）大鼠等不同近交系杂交产生的分离群体中大鼠的内皮素-1和内皮素-3基因型。给分离群体喂食高（8%）氯化钠饮食。通过方差分析确定基因型与血压或相对心脏重量的连锁关系。通过对一组重组近交系进行基因分型确定大鼠内皮素-3基因的染色体定位。
鉴定出内皮素-1基因的两个等位基因和内皮素-3基因的三个等位基因。内皮素-1位点与血压或相对心脏重量不共分离。在内皮素-3位点在SS/Jr×F1（SS/Jr×SR/Jr）群体中与血压和相对心脏重量共分离，但在含有较高比例SR/Jr品系基因的群体中不共分离。内皮素-3和精囊蛋白-1位点连锁并位于大鼠3号染色体上。
内皮素-3基因是或与3号染色体上的一个位点连锁，该位点调节近交系Dahl大鼠的血压和相对心脏重量，且这些效应强烈依赖于遗传背景。
