Time-course genetic analysis of albuminuria in Dahl salt-sensitive rats on low-salt diet
Time-course genetic analysis of albuminuria in Dahl salt-sensitive rats on low-salt diet
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DOI：
10.1097/01.asn.0000060572.13794.58
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发表时间：
2003-05-01
影响因子：
13.6
通讯作者：
Rapp, JP
中科院分区：
文献类型：
--
作者：
Garrett, MR;Dene, H;Rapp, JP
达尔盐敏感型高血压(S)大鼠在生命早期就出现蛋白尿，即使在低盐饮食下也是如此。相比之下，自发性高血压大鼠(SHR)尽管血压升高，但对蛋白尿的抵抗力很强。S与自发性高血压杂种F-1表现出与自发性高血压相似的低尿白蛋白排泄率(UAE)和低尿蛋白排泄率(UPE)，即以自发性高血压大鼠为主。对F-1代大鼠与隐性S品系回交获得的一个大群体(n=276)进行了遗传分析。在8、12和16周龄进行的基因组扫描在9条大鼠染色体(RNO)上产生了10个UAE和/或UPE的数量性状基因座(QTL)，即RNO1、RNO2、RNO6、RNO8、RNO9、RNO10、RNO11、RNO13和RNO19。RNO6上有两个Upe QTL。在大多数UAE和/或Upe QTL中，S等位基因与排泄量增加有关，但在RNO6和RNO11上的一个QTL上，S等位基因导致排泄量减少。只有RNO10上的阿联酋和Upe QTL与一个BP QTL共定位。RNO10上的S等位基因导致了较高的血压和较高的UAE。在RNO1和RNO6上检测到另外两个BP QTL。大部分UAE和UPE QTL与S大鼠肾脏病变特征QTL共定位。观察到阿联酋存在多种相互作用，其中许多涉及RNO2。综上所述，UAE是高度多基因的，并且大多数改变UAE的QTL并不与BP的QTL共定位，正如BP的尾袖测量所评估的那样。
The Dahl salt-sensitive hypertensive (S) rat develops albuminuria early in life even on a low-salt diet. In contrast, the spontaneously hypertensive rat (SHR) is highly resistant to developing albuminuria despite elevated BP. An F-1 hybrid of S and SHR showed a low urinary albumin excretion (UAE) and low urinary protein excretion (UPE) similar to SHR, i.e., SHR was dominant. A genetic analysis was carried out on a large population (n = 276) obtained by backcrossing F-1 rats to the recessive S strain; the population was fed a low-salt diet. Genome scans done at 8, 12, and 16 wk of age yielded ten quantitative trait loci (QTL) for UAE and/or UPE with variable time-course patterns on nine rat chromosomes (RNO), i.e., RNO1, RNO2, RNO6, RNO8, RNO9, RNO10, RNO11, RNO13, and RNO19. There were two UPE QTL on RNO6. At most of the UAE and/or UPE QTL, the S allele was associated with increased excretion, except for one of the QTL on RNO6 and the QTL on RNO11, where the S allele caused decreased excretion. Only the UAE and UPE QTL on RNO10 co-localized with a BP QTL. The S allele on RNO10 caused higher BP and higher UAE. Two additional BP QTL were detected on RNO1 and RNO6. Most of the UAE and UPE QTL colocalized with QTL for kidney lesions characteristic of S rats. Multiple interactions were observed for UAE, many of which involved RNO2. In summary, UAE is highly polygenic and the majority of the QTL altering UAE do not co-localize with QTL for BP as evaluated by tail-cuff measurements of BP.