Koike G, Krieger J E, Jacob H J, Mukoyama M, Pratt R E, Dzau V J
Falk Cardiovascular Research Center, Stanford University School of Medicine, CA 94305-5246.
Biochem Biophys Res Commun. 1994 Jan 14;198(1):380-6. doi: 10.1006/bbrc.1994.1053.
Using genetic mapping approaches, a gene on chromosome 10, Bp1, has been identified in the stroke-prone spontaneously hypertensive rat (SHRSP) in the same region that contains the gene for angiotensin converting enzyme (ACE). Since ACE plays an important role in blood pressure regulation, the ACE gene is a leading candidate for Bp1. To examine the possibility that a structural abnormality of ACE exists in the SHRSP, we cloned and characterized the cDNAs for the Wistar-Kyoto rat (WKY) and SHRSP ACE. Both cDNAs encode a single polypeptide of 1,313 amino acid residues with an estimated molecular weight of 150.9 KDa. Five nucleotide differences were identified between the WKY and the SHRSP ACE cDNAs. One of these differences resulted in an amino acid substitution (Lys-207 in the WKY to Arg-207 in the SHRSP). But the enzymatic properties of partially purified ACE from the two strains were similar. Thus the data suggest that an alteration in the primary structure of rat ACE does not contribute to the hypertension in the SHRSP.
运用基因定位方法，在易患中风的自发性高血压大鼠（SHRSP）的10号染色体上，已在与血管紧张素转换酶（ACE）基因相同的区域鉴定出一个基因Bp1。由于ACE在血压调节中起重要作用，所以ACE基因是Bp1的主要候选基因。为了研究SHRSP中是否存在ACE结构异常的可能性，我们克隆并鉴定了Wistar-Kyoto大鼠（WKY）和SHRSP的ACE的cDNA。两种cDNA均编码一种由1313个氨基酸残基组成的单一多肽，估计分子量为150.9 kDa。在WKY和SHRSP的ACE cDNA之间鉴定出五个核苷酸差异。其中一个差异导致氨基酸替换（WKY中的Lys-207替换为SHRSP中的Arg-207）。但是从这两个品系中部分纯化的ACE的酶学性质相似。因此，数据表明大鼠ACE一级结构的改变与SHRSP的高血压无关。
