Chromosome substitution modulates resistance to ischemia reperfusion injury in Brown Norway rats.
Chromosome substitution modulates resistance to ischemia reperfusion injury in Brown Norway rats.
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DOI：
10.1038/ki.2012.391
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发表时间：
2013-02
影响因子：
19.6
通讯作者：
中科院分区：
文献类型：
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棕色挪威大鼠（BN，BN/NHsdMcwi）对缺血再灌注后发生急性肾损伤（阿基）具有深刻的抵抗力。为了帮助确定这种耐药性的遗传基础，我们使用了consomic大鼠，其中将BN大鼠的单个染色体置于Dahl SS大鼠（SS，SS/JrHsdMcwi）的遗传背景中，以确定哪些染色体含有有助于保护免受阿基的等位基因。亲本菌株对缺血再灌注的敏感性显著不同，SS和BN缺血45分钟和再灌注24小时后血浆肌酐水平分别为4.1和1.3 mg/dl。没有consomic菌株表现出类似于亲本BN菌株的保护作用。9个同源株（SS-7 BN、SS-XBN、SS-8BN、SS-4 BN、SS-15 BN、SS-3BN、SS-10 BN、SS-6 BN和SS-5 BN）显示部分保护（血浆肌酐约2.5-3.0 mg/dl），表明多个等位基因导致阿基的严重程度。使用疾病本体数据库术语和大鼠基因组数据库中BN染色体上的肾功能数量性状基因座进行计算机模拟分析，从而提供对阿基的部分保护。这种策略确定了至少36个候选基因，其中几个先前与阿基的病理生理学有关。因此，这些等位基因的天然变体或这些染色体上尚待鉴定的等位基因提供针对阿基的保护。这些等位基因可能是易感患者人群中阿基的潜在调节剂。
Brown Norway rats (BN, BN/NHsdMcwi) are profoundly resistant to developing acute kidney injury (AKI) following ischemia reperfusion. To help define the genetic basis for this resistance, we used consomic rats, in which individual chromosomes from BN rats were placed into the genetic background of Dahl SS rats (SS, SS/JrHsdMcwi) to determine which chromosomes contain alleles contributing to protection from AKI. The parental strains had dramatically different sensitivity to ischemia reperfusion with plasma creatinine levels following 45 minutes of ischemia and 24 hours reperfusion of 4.1 and 1.3 mg/dl in SS and in BN, respectively. No consomic strain showed protection similar to the parental BN strain. Nine consomic strains (SS-7BN, SS-XBN, SS-8BN, SS-4BN, SS-15BN, SS-3BN, SS-10BN, SS-6BN, and SS-5BN) showed partial protection (plasma creatinine about 2.5-3.0 mg/dl), suggesting that multiple alleles contribute to the severity of AKI. In silico analysis was performed using disease ontology database terms and renal function quantitative trait loci from the rat genome database on the BN chromosomes giving partial protection from AKI. This tactic identified at least 36 candidate genes, with several previously linked to the pathophysiology of AKI. Thus, natural variants of these alleles or yet to be identified alleles on these chromosomes provide protection against AKI. These alleles may be potential modulators of AKI in susceptible patient populations.
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影响因子：
13.6
作者：
Perianayagam, Mary C.;Liangos, Orfeas;Jaber, Bertrand L.
通讯作者：
Jaber, Bertrand L.
影响因子：
3.8
作者：
Guo, Shuhong;Wharton, Walker;Shi, Honglian
通讯作者：
Shi, Honglian
影响因子：
19.6
作者：
Bonventre, JV;Zuk, A
通讯作者：
Zuk, A
影响因子：
8.3
作者：
Cowley, AW;Roman, RJ;Jacob, HJ
通讯作者：
Jacob, HJ
影响因子：
--
作者：
EMAMI, A;SCHWARTZ, JH;BORKAN, SC
通讯作者：
BORKAN, SC