MOLECULAR GENETIC ANALYSIS OF BLOOD PRESSURE IN THE RAT

我的长期目标是识别和描述导致 不同品系高血压病患者的血压差异 血压正常的大鼠。这项工作是理解其作用机制的基础。 人类遗传性高血压。 这里主要关注的是肾素基因。我已经建立了重要的影响 Dahl盐性高血压患者肾素等位基因的血压研究 敏感(S)大鼠和Dahl耐盐高血压(R)大鼠。肾素 这些菌株携带的等位基因，分别命名为S和r。 在基因实验中与血压共分离。对…的影响 我最近发现的另外两个肾素等位基因的血压 将通过将每个新的等位基因与S的等位基因进行比较来评估。这是 通过确定血压的某一组分是否与 来自Dahl盐敏感的F2群体中的新肾素等位基因 (S)大鼠和一种携带新等位基因的菌株。关于的结构信息 已知的肾素等位基因将被扩展，并搜索其他 在更多品系的老鼠中存在等位基因。 将进行转基因实验以确定S和r肾素 等位基因实际上是导致血压差异的原因。候补方案 可能是这些S和r肾素等位基因与血液共分离 压力，因为它们与一个未知的基因相关联，事实上，该基因导致 血压差。S和r肾素等位基因将插入 利用转基因技术培育盐敏感(S)大鼠品系。这将是 允许评估这些等位基因对血压的影响 独立于连锁的基因座。S和r肾素等位基因的成分可以是 在通过转基因插入的DNA构建物中交换，以便 定位这些等位基因中的DNA多态，这在 造成血压变化。 最后，肾素-血管紧张素系统的其他组成部分(血管紧张素原， 转换酶，由ma癌基因编码的血管紧张素受体)将 评估大鼠品系之间的DNA多态，以及 多态基因将被测试是否与血压存在协同隔离。

My long-term goal is to identify and describe the genes which cause differences in blood pressure among various strains of hypertensive and normotensive rats. This work is basic to understanding the mechanism of genetic hypertension in man. The main focus here is the renin gene. I have established important effects on blood pressure for the renin alleles from Dahl salt-hypertension sensitive (S) rats and Dahl salt-hypertension resistant (R) rats. Renin alleles carried by these strains, designated s and r respectively, cosegregated with blood pressure in genetic experiments. The effect on blood pressure of two additional renin alleles that I have recently found will be evaluated by comparing each new allele to the s allele. This is done by determining if a component of blood pressure cosegregates with a given new renin allele in an F2 population derived from Dahl salt-sensitive (S) rats and a strain carrying the new allele. Structural information on the known renin alleles will be extended and a search made for additional alleles in more strains of rats. Transgenic experiments will be performed to determine if the s and r renin alleles are actually causing differences in blood pressure. The alternate possibility is that these s and r renin alleles cosegregate with blood pressure because they are linked to an unknown locus that, in fact, causes the blood pressure differences. s and r renin alleles will be inserted in the salt-sensitive (S) rat strain using transgenic techniques. This will allow evaluation of the blood pressure altering effects of these alleles independent of linked loci. Components of the s and r renin alleles can be exchanged in DNA constructs that are inserted transgenically in order to localize 'the' DNA polymorphism within these alleles that is important in creating blood pressure changes. Lastly, other components of the renin-angiotensin system (angiotensinogen, converting enzyme, the angiotensin receptor coded by the mas oncogene) will be evaluated for DNA polymorphisms among rat strains, and such polymorphisms will be tested for cosegregation with blood pressure.