Identification of quantitative trait loci for cardiac hypertrophy in two different strains of the spontaneously hypertensive rat
Identification of quantitative trait loci for cardiac hypertrophy in two different strains of the spontaneously hypertensive rat
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DOI：
10.1291/hypres.28.273
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发表时间：
2005-03-01
影响因子：
5.4
通讯作者：
Kato, N
中科院分区：
文献类型：
--
作者：
Inomata, H;Watanabe, T;Kato, N
已知心脏肥大和左心室肥大实质上受遗传因素控制。作为一个实验模型，我们进行了全基因组筛选的F-2人口的心脏质量从中风倾向的自发性高血压大鼠（SHRSP）和正常的自发性高血压大鼠（SHR）和Wistar京都大鼠（WKY）的日本殖民地。独立产生两个F-2队列：F-2（SHRSP x WKY）（110只雄性和110只雌性大鼠）和F2（SHR x WKY）（151只雄性大鼠）。在盐负荷7个月后的12个月龄时，评估F2（SHRSP x WKY）的心脏重量与体重的比率（Hw/Bw），并且在喂食正常大鼠食物饮食的F-2（SHR x WKY）的大约15周龄时评估心脏重量与体重的比率（Hw/Bw）。在F-2（SHRSP x WKY）雄性后代中用251个标记进行初步筛选之后，在F-2（SHRSP x WKY）雌性后代和F-2（SHR x WKY）雄性后代中分别选择170个和161个标记并进行表征。来自四个染色体区域的标记显示出与Hw/Bw的暗示或显著连锁。在大鼠染色体（RNO）3上的D3 Mgh 16附近发现了最强和最一致的连锁（在所研究的F-2群体中，最大对数的比值分数达到4.0至6.6）。在RNO 6、RNO 10和RNO 13上的其他三个区域中，无论是男性还是女性，连锁程度都更突出。这些数据提供了坚实的证据，一个“主要”RNO 3的数量性状基因座调节Hw/Bw在SHRSP和SHR，也表明可能存在性二型性心脏肥大的遗传易感性。
Cardiac hypertrophy and left ventricular hypertrophy are known to be substantially controlled by genetic factors. As an experimental model, we undertook genome-wide screens for cardiac mass in F-2 populations bred from the stroke-prone spontaneously hypertensive rats (SHRSP) and normal spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) of a Japanese colony. Two F-2 cohorts were independently produced: F-2(SHRSP x WKY) (110 male and 110 female rats) and F2(SHR x WKY) (151 male rats). The ratio of heart weight to body weight (Hw/Bw) was evaluated at 12 months of age in F2(SHRSP x WKY) after salt-loading for 7 months, and at around 15 weeks of age in F-2(SHR x WKY) who had been fed a normal rat chow diet. Subsequent to an initial screen with 251 markers in F-2(SHRSP x WKY) male progeny, 170 and 161 markers were selected and characterized in F-2(SHRSP x WKY) female progeny and F-2(SHR x WKY) male progeny, respectively. Markers from four chromosomal regions showed suggestive or significant linkage to Hw/Bw. The strongest and the most consistent linkage was found in the vicinity of D3Mgh16 on rat chromosome (RNO) 3 (a maximal log of the odds score reached 4.0 to 6.6 across the F-2 populations studied). In the other three regions on RNO6, RNO10 and RNO13, the degree of linkage was more prominent in either males or females. These data provide solid evidence for a "principal" RNO3 quantitative trait loci regulating Hw/Bw in SHRSP and SHR, and also suggest the possible presence of sexual dimorphism in regard to genetic susceptibility for cardiac hypertrophy.