MOLECULAR GENETIC ANALYSIS OF BLOOD PRESSURE IN THE RAT

我的长期目标是找出并描述导致 不同高血压菌株之间的血压差异， 正常血压大鼠。这项工作是了解 男性遗传性高血压 这里的主要焦点是肾素基因。我已经建立了重要影响 Dahl盐性高血压的肾素等位基因对血压的影响 敏感（S）大鼠和Dahl盐-高血压抵抗（R）大鼠。肾素 这些菌株携带的等位基因，分别命名为S和R， 在遗传实验中与血压共分离。的影响 我最近发现的另外两个肾素等位基因， 将通过将每个新等位基因与s等位基因进行比较来评估。这是 通过确定血压的一个组成部分是否与 在来自Dahl盐敏感型的F2群体中给定新的肾素等位基因， (S)老鼠和携带新等位基因的品系。结构信息 已知的肾素等位基因将被扩展，并搜索额外的 在更多品系的老鼠身上发现了等位基因。 将进行转基因实验以确定s和r肾素 等位基因实际上导致了血压的差异。备用 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位点有关，事实上， 血压差异。s和r肾素等位基因将被插入到 盐敏感（S）大鼠品系使用转基因技术。这将 允许评估这些等位基因的血压改变效应 与连锁基因座无关。s和r肾素等位基因的组分可以是 在DNA构建体中交换，所述DNA构建体被转基因地插入， 在这些等位基因中定位DNA多态性， 造成血压变化。 最后，肾素-血管紧张素系统的其它组分（血管紧张素原， 转换酶，即由MAS癌基因编码的血管紧张素受体）将 评估大鼠品系之间的DNA多态性， 将测试多态性与血压的共分离。

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.