Orlov S N, Dutil J, Hamet P, Deng A Y
Research Centre, Centre Hospitalier de l'Université de Montreal, Hôtel Dieu, Montreal, Quebec, H2W 1T8, Canada.
Physiol Genomics. 2001 Dec 21;7(2):171-7. doi: 10.1152/physiolgenomics.00059.2001.
Both linkage and use of congenic strains have shown that a chromosome region near the gene for the Na-K-ATPase alpha(1)-subunit (Atp1a1) contained a quantitative trait locus (QTL) for blood pressure (BP). Currently, two congenic strains, designated S.M5 and S.M6, were made by replacing a segment of the Dahl salt-sensitive SS/Jr (S) rat by the homologous region of the Milan normotensive rat (MNS). In S.M5, the gene for Atp1a1 is from the MNS strain; whereas in S.M6, Atp1a1 is from the S strain. The baseline activity of the alpha(1)-Na-K-ATPase and its stoichiometry were evaluated by an assay of ouabain-sensitive inwardly and outwardly directed (86)Rb and (22)Na fluxes in erythrocytes. The two congenic strains showed a similar BP, but both had a BP lower than that of S rats (P < 0.0001). Neither the alpha(1)-Na-K-ATPase activity nor its stoichiometry was affected by the substitution of the Atp1a1 alleles of S by those of MNS. Thus the BP-lowering effects observed in S.M5 and S.M6 could not be attributed to the alpha(1)-Na-K-ATPase activity or its stoichiometry. Atp1a1 is not supported as a candidate to be a BP QTL.
连锁分析和同源近交系的应用均表明，钠钾ATP酶α(1)亚基（Atp1a1）基因附近的一个染色体区域包含血压（BP）的数量性状基因座（QTL）。目前，通过用米兰正常血压大鼠（MNS）的同源区域替换Dahl盐敏感型SS/Jr（S）大鼠的一段区域，构建了两个同源近交系，分别命名为S.M5和S.M6。在S.M5中，Atp1a1基因来自MNS品系；而在S.M6中，Atp1a1来自S品系。通过测定红细胞中哇巴因敏感的内向和外向（86）Rb和（22）Na通量，评估α(1)-钠钾ATP酶的基线活性及其化学计量。这两个同源近交系的血压相似，但均低于S大鼠（P < 0.0001）。用MNS的Atp1a1等位基因替换S的Atp1a1等位基因，既不影响α(1)-钠钾ATP酶的活性，也不影响其化学计量。因此，在S.M5和S.M6中观察到的血压降低效应不能归因于α(1)-钠钾ATP酶的活性或其化学计量。Atp1a1不被认为是血压QTL的候选基因。
