Investigating the effect of genetic background on proteinuria and renal injury using two hypertensive strains.
Investigating the effect of genetic background on proteinuria and renal injury using two hypertensive strains.
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使用两种高血压菌株研究遗传背景对蛋白尿和肾损伤的影响。
DOI：
10.1152/ajprenal.90370.2008
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Garrett,MichaelR
中科院分区：
文献类型：
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作者：
Packard,Matthew;Saad,Yasser;Gunning,WilliamT;Gupta,Shalini;Shapiro,Joseph;Garrett,MichaelR
早期对Dahl盐敏感型高血压(S)和自发性高血压大鼠（SHR）进行的连锁分析确定了10个与肾脏和/或心血管特征相关的基因组区域。特别是，大鼠染色体（RNO） 8和13上的位点与蛋白尿、蛋白尿和肾损伤有关。在这两个位点上，S等位基因与蛋白尿增加和肾损害有关。本研究旨在证实连锁分析，并评估遗传背景对每个基因座（RNO8或RNO13）在易感（S大鼠）或耐药（SHR）遗传背景下对肾脏疾病发展产生表型差异的能力的影响。同源菌株可以将RNO8或RNO13的基因组片段从SHR转移到S遗传背景中[S]。SHR或S.SHR]可显著减少蛋白尿和改善肾功能。两种同源菌株均表现出肾小球和肾小管损伤明显减轻，与S相比，肾间质纤维化是主要的病理差异。相反，RNO8或RNO13基因组区域从S转移到耐药SHR遗传背景[SHR]。S或SHR。S]与SHR相比，蛋白尿、肾小球、肾小管或间质损伤无显著差异。这些发现表明，遗传环境在影响蛋白尿RNO8和RNO13的基因表型表达中起着重要的作用。
An earlier linkage analysis conducted on a population derived from the Dahl salt-sensitive hypertensive (S) and the spontaneously hypertensive rat (SHR) identified 10 genomic regions linked to several renal and/or cardiovascular traits. In particular, loci on rat chromosomes (RNO) 8 and 13 were linked to proteinuria, albuminuria, and renal damage. At both loci, the S allele was associated with increased proteinuria and renal damage. The current study aimed to confirm the linkage analysis and to evaluate the effect of genetic background on the ability of each locus (either RNO8 or RNO13) to exert a phenotypic difference when placed on a genetic background either susceptible (S rat) or resistant (SHR) to the development of renal disease. Congenic strains developed to transfer genomic segments from either RNO8 or RNO13 from the SHR onto the S genetic background [S.SHR or S.SHR] demonstrated significantly reduced proteinuria and improved renal function. Both congenic strains demonstrated significantly reduced glomerular and tubular injury, with renal interstitial fibrosis as the predominant pathological difference compared with the S. In contrast, transfer of RNO8 or RNO13 genomic regions from the S onto the resistant SHR genetic background [SHR.S or SHR.S] yielded no significant difference in proteinuria or glomerular, tubular, or interstitial injury compared with SHR. These findings demonstrate that genetic context plays a significant and important role in the phenotypic expression of genes influencing proteinuria on RNO8 and RNO13.