Herlan Laura, Schulz Angela, Schulte Leonard, Schulz Herbert, Hübner Norbert, Kreutz Reinhold
Department of Clinical Pharmacology and Toxicology, CharitéCenter 4 - Therapy and Research, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Max-Delbrück Center for Molecular Medicine, Berlin, Germany.
Clin Exp Pharmacol Physiol. 2015 Oct;42(10):1051-8. doi: 10.1111/1440-1681.12462.
Defects in nephrogenesis can have detrimental effects on cardiovascular and renal health in adult life. This is confirmed by observations in the Munich Wistar Frömter (MWF) rat that exhibits a congenital nephron deficit and renal failure with age. Here, we performed genome-wide transcriptome analysis in embryonic kidneys to identify candidate genes for the reduced nephron number in MWF. We compared MWF rats at embryonic day (E)15.5 with stage-matched spontaneously hypertensive rats (SHR) at E16. Microarray analysis revealed 311 transcripts representing 253 known genes with differential expression between MWF and SHR (fold change > +1.5 or < -1.5, respectively). Genes located on rat chromosome (RNO) 6 were of special interest because RNO6 carries genetic loci previously linked to the nephron deficit and renal damage in MWF. Differentially expressed genes located on RNO6 were further investigated by Real-time PCR including the late-stage of fetal kidney development, i.e. E19.0/E19.5, and week 4 of postnatal life when nephrogenesis is completed. Seven genes including Abcg5, Ab1-233, Efcab11, Fntb, Gpx2, Lrrn3, and Rtn1 were assigned on RNO6 and their differential expression was confirmed. Thus, we identified several genes that may act as crucial players in nephron development and are responsible for the nephron deficit in the MWF model.
肾发生缺陷可能会对成年后的心血管和肾脏健康产生不利影响。慕尼黑威斯塔弗罗姆特（MWF）大鼠的观察结果证实了这一点，该大鼠表现出先天性肾单位缺陷，并随着年龄增长出现肾衰竭。在这里，我们对胚胎肾脏进行了全基因组转录组分析，以确定MWF中肾单位数量减少的候选基因。我们将胚胎第15.5天（E15.5）的MWF大鼠与E16阶段匹配的自发性高血压大鼠（SHR）进行了比较。微阵列分析显示，有311个转录本代表253个已知基因，在MWF和SHR之间存在差异表达（倍数变化分别> +1.5或< -1.5）。位于大鼠6号染色体（RNO）上的基因特别受关注，因为RNO6携带了先前与MWF中的肾单位缺陷和肾损伤相关的基因座。通过实时PCR对位于RNO6上的差异表达基因进行了进一步研究，包括胎儿肾脏发育的后期阶段，即E19.0/E19.5，以及出生后第4周肾发生完成时。包括Abcg5、Ab1-233、Efcab11、Fntb、Gpx2、Lrrn3和Rtn1在内的7个基因被定位在RNO6上，并证实了它们的差异表达。因此，我们确定了几个可能在肾单位发育中起关键作用并导致MWF模型中肾单位缺陷的基因。
