Which Sry locus is the hypertensive Y chromosome locus?
Which Sry locus is the hypertensive Y chromosome locus?
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哪个Sry位点是高血压Y染色体位点？
DOI：
10.1161/hypertensionaha.108.124131
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Milsted,Amy
中科院分区：
文献类型：
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作者：
Turner,MonteE;Farkas,Joel;Dunmire,Jeff;Ely,Daniel;Milsted,Amy
自发性高血压大鼠(SHR)的Y染色体包含一种遗传成分，与Wistar-京都(WKY)Y染色体相比，Y染色体会使血压升高。这项研究测试了Sry基因复合体作为SHR Y染色体的高血压成分。对1个Y染色体高血压株(SHR/Akr)和2个Y染色体正常株(SHR/CRL和WKY/Akr)的Sry基因座进行了测序。SHR株和WKY株有7个Sry基因座，而WKY株有6个Sry基因座。SHR和WKY株之间共有的6个基因座在比较的序列中是相同的(编码区，392个碱基5‘端，3’端1200个碱基)。这两个SHR株都有一个在WKY大鼠中未发现的基因(Sry3)，但SHR/Akr和SHR/CRL大鼠的Sry3基因不同。SHR菌株间的Sry3基因有6个突变，而其他6个Sry基因座是相同的。如果Sry3是Y染色体高血压组分，SHR/CRL中SHR特有的基因座和该基因座上的突变模式与Y染色体高血压的丢失是一种预期的模式。SHR/y品系在4-15周龄肾脏中的总Sry表达显著增加。Sry在肾上腺和肾脏中的表达有显着差异(肾脏高出15-30倍)，但不同品系之间没有显着差异。这些结果以及以前的研究表明，Sry与酪氨酸羟化酶启动子相互作用，并通过外源Sry表达升高血压，表明Sry基因座是SHR Y染色体的高血压成分。
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.