Turner Monte E, Farkas Joel, Dunmire Jeff, Ely Daniel, Milsted Amy
Department of Biology, University of Akron, Akron, OH 44325-3908, USA.
Hypertension. 2009 Feb;53(2):430-5. doi: 10.1161/HYPERTENSIONAHA.108.124131. Epub 2008 Dec 15.
The Y chromosome of the spontaneously hypertensive rat (SHR) contains a genetic component that raises blood pressure compared with the Wistar-Kyoto (WKY) Y chromosome. This research tests the Sry gene complex as the hypertensive component of the SHR Y chromosome. The Sry loci were sequenced in 1 strain with a hypertensive Y chromosome (SHR/Akr) and 2 strains with a normotensive Y chromosome (SHR/Crl and WKY/Akr). Both SHR strains have 7 Sry loci, whereas the WKY strain has 6. The 6 loci in common between SHR and WKY strains were identical in the sequence compared (coding region, 392-bp 5' prime flanking, 1200-bp 3' flanking). Both SHR strains have a locus (Sry3) not found in WKY rats, but this locus is different between SHR/Akr and SHR/Crl rats. Six mutations have accumulated in Sry3 between the SHR strains, whereas the other 6 Sry loci are identical. This pattern of an SHR-specific locus and mutation in this locus in SHR/Crl coinciding with the loss of Y chromosome hypertension is an expected pattern if Sry3 is the Y chromosome-hypertensive component. The SHR/y strain showed a significant increase in total Sry expression in the kidney between 4 and 15 weeks of age. There are significant differences in Sry expression between adrenal glands and the kidney (15 to 30 times higher in kidneys) but no significant differences between strains. These results, along with previous studies demonstrating an interaction of Sry with the tyrosine hydroxylase promoter and increased blood pressure with exogenous Sry expression, suggest the Sry loci as the hypertensive component of the SHR Y chromosome.
自发性高血压大鼠(SHR)的Y染色体含有一种遗传成分,与Wistar-Kyoto(WKY)Y染色体相比,该成分会升高血压。本研究将Sry基因复合体作为SHR Y染色体的高血压成分进行检测。对1个具有高血压Y染色体的品系(SHR/Akr)和2个具有正常血压Y染色体的品系(SHR/Crl和WKY/Akr)的Sry基因座进行了测序。两个SHR品系均有7个Sry基因座,而WKY品系有6个。SHR和WKY品系共有的6个基因座在比较的序列中是相同的(编码区、392 bp的5'侧翼、1200 bp的3'侧翼)。两个SHR品系都有一个在WKY大鼠中未发现的基因座(Sry3),但该基因座在SHR/Akr和SHR/Crl大鼠之间是不同的。在SHR品系之间,Sry3中积累了6个突变,而其他6个Sry基因座是相同的。如果Sry3是Y染色体高血压成分,那么SHR特异性基因座以及SHR/Crl中该基因座的突变与Y染色体高血压丧失相吻合的这种模式是预期的模式。SHR/y品系在4至15周龄时肾脏中Sry的总表达显著增加。肾上腺和肾脏之间的Sry表达存在显著差异(肾脏中高15至30倍),但品系之间无显著差异。这些结果,连同先前证明Sry与酪氨酸羟化酶启动子相互作用以及外源性Sry表达会升高血压的研究,表明Sry基因座是SHR Y染色体的高血压成分。