Department of Clinical Pharmacology and Toxicology, Charité Centrum für Therapieforschung, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Hypertens Res. 2012 Jul;35(7):675-94. doi: 10.1038/hr.2012.77. Epub 2012 May 31.
During the last two decades, significant progress in our understanding of the development of kidney diseases has been achieved by unravelling the mechanisms underlying rare familial forms of human kidney diseases. Due to the genetic heterogeneity in human populations and the complex multifactorial pathogenesis of the disease phenotypes, the dissection of the genetic basis of common chronic kidney diseases (CKD) remains a difficult task. In this regard, several inbred rat models provide valuable complementary tools to uncover the genetic basis of complex renal disease phenotypes that are related to common forms of CKD. In this review, data obtained in nine experimental rat models, including the Buffalo (BUF), Dahl salt-sensitive (SS), Fawn-hooded hypertensive (FHH), Goto-Kakizaki (GK), Lyon hypertensive (LH), Munich Wistar Frömter (MWF), Sabra hypertension-prone (SBH), spontaneously hypertensive rat (SHR) and stroke-prone spontaneously hypertensive rat (SHRSP) inbred strains, that contributed to the genetic dissection of renal disease phenotypes are presented. In this panel of inbred strains, a large number of quantitative trait loci (QTL) linked to albuminuria/proteinuria and other functional or structural kidney abnormalities could be identified by QTL mapping analysis and follow-up studies including consomic and congenic rat lines. The comprehensive exploitation of the genotype-renal phenotype associations that are inherited in this panel of rat strains is suitable for making a significant contribution to the development of an integrated approach to the systems genetics of common CKD.
在过去的二十年中，通过揭示人类肾脏疾病罕见家族形式的发病机制，我们在理解肾脏疾病的发展方面取得了重大进展。由于人类群体中的遗传异质性和疾病表型的复杂多因素发病机制，常见慢性肾脏病（CKD）的遗传基础的剖析仍然是一项艰巨的任务。在这方面，几种近交系大鼠模型提供了有价值的补充工具，可以揭示与常见 CKD 形式相关的复杂肾脏疾病表型的遗传基础。在这篇综述中，介绍了从九个实验大鼠模型中获得的数据，包括布法罗（BUF）、道尔盐敏感（SS）、法恩霍德高血压（FHH）、高田-卡基扎基（GK）、莱昂高血压（LH）、慕尼黑维斯塔弗里蒙特（MWF）、萨布拉高血压易患（SBH）、自发性高血压大鼠（SHR）和易发生中风的自发性高血压大鼠（SHRSP）近交系，这些模型为肾脏疾病表型的遗传剖析做出了贡献。在这个近交系大鼠的面板中，通过 QTL 映射分析和包括同源和同基因大鼠系在内的后续研究，可以确定与白蛋白尿/蛋白尿和其他功能或结构肾脏异常相关的大量数量性状基因座（QTL）。充分利用该大鼠品系中遗传的基因型-肾脏表型关联，适合为常见 CKD 的系统遗传学综合方法的发展做出重大贡献。
