Ohno Y, Matsuo K, Suzuki H, Tanase H, Ikeshima H, Takano T, Saruta T
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
J Hypertens. 1996 Mar;14(3):287-91. doi: 10.1097/00004872-199603000-00003.
To search for a genetic marker of the sarco(endo)plasmic reticulum Ca(2+)-dependent ATPase (SERCA) II gene in spontaneously hypertensive rats (SHRs) and to investigate differences in blood pressure and intracellular Ca2+ among some substrains of SHRs and Wistar-Kyoto (WKY) rats related to their SERCA II genotypes.
The coding region of the SERCA II gene was sequenced in SHRs. Blood pressure and intracellular Ca2+ concentration ([Ca2+]i) in platelets were measured in substrains of SHRs and WKY rats with different SERCA II genotypes.
A point mutation that provided restriction fragment length polymorphisms (RFLPs) by HindIII or Saul was found in the SERCA II gene. The polymerase chain reaction (PCR) products were digested by HindIII in SHR substrains and WKY-Kyoto rats, whereas they were digested by Saul in normotensive strains and SHR-Toho. Among SHR-Kyoto, SHR-Toho, WKY-Kyoto and WKY-Charles River, the substrains with the HindIII-digested SERCA II genotype showed slightly but significantly higher systolic blood pressure and augmented agonist-stimulated [Ca2+]i than those with the Saul-digested genotype.
RFLPs were found in the SERCA II gene. In the substrain analysis of SHRs and WKY rats, higher blood pressure and increased [Ca2+]i were associated with the SERCA II genotype digested by HindIII. The SERCA II gene locus has the potential to contribute to the development of hypertension and abnormal intracellular Ca2+ metabolism in SHRs. These RFLPs in the SERCA II gene should be a useful genetic marker.
寻找自发性高血压大鼠（SHR）肌浆（内质）网Ca（2+）依赖性ATP酶（SERCA）II基因的遗传标记，并研究SHR某些亚系和Wistar-Kyoto（WKY）大鼠中与SERCA II基因型相关的血压和细胞内Ca2+差异。
对SHR的SERCA II基因编码区进行测序。在具有不同SERCA II基因型的SHR亚系和WKY大鼠中测量血小板中的血压和细胞内Ca2+浓度（[Ca2+]i）。
在SERCA II基因中发现了一个点突变，该突变通过HindIII或Saul产生限制性片段长度多态性（RFLP）。聚合酶链反应（PCR）产物在SHR亚系和WKY-Kyoto大鼠中被HindIII消化，而在正常血压品系和SHR-Toho中被Saul消化。在SHR-Kyoto、SHR-Toho、WKY-Kyoto和WKY-Charles River中，具有HindIII消化的SERCA II基因型的亚系收缩压略高但显著高于具有Saul消化基因型的亚系，且激动剂刺激的[Ca2+]i增加。
在SERCA II基因中发现了RFLP。在SHR和WKY大鼠的亚系分析中，较高的血压和[Ca2+]i增加与被HindIII消化的SERCA II基因型相关。SERCA II基因位点有可能导致SHR高血压的发展和细胞内Ca2+代谢异常。SERCA II基因中的这些RFLP应该是一个有用的遗传标记。
