Parent-of-origin effects on cardiac response to pressure overload in mice
Parent-of-origin effects on cardiac response to pressure overload in mice
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DOI：
10.1152/ajpheart.00896.2008
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发表时间：
2009-09-01
影响因子：
4.8
通讯作者：
Smyth, Susan S.
中科院分区：
文献类型：
--
作者：
Barrick, Cordelia J.;Dong, Anping;Smyth, Susan S.
巴里克CJ，东A，怀克尔R，玉米D，杨F，Threadgill DW，史密斯SS。母体药物对小鼠压力超负荷心脏反应的影响。Am J Physiol Heart Circ Physiol 297：H1003-H1009，2009.首次发表于2009年6月26日; doi：10.1152/ajpheart.00896.2008。左心室肥厚是心血管死亡的独立危险因素，通常由高血压引起。在啮齿类动物中，主动脉横缩窄（TAC）是LV对压力超负荷反应的机制研究中经常采用的模型。我们以前报道过，近交系雄性小鼠对TAC表现出不同的心脏反应，C57 BL/6 J（B6）出现LV扩张和收缩力受损，129 S1/SvImJ（129）雄性显示同心LVH。在本研究中，我们通过比较雌性B6和雌性129小鼠以及B6和129小鼠（B6129 F1和129 B6 F1）之间相互杂交的F1后代的心脏功能、器官重量、心脏肥大标志物表达和组织学，研究了性别和亲本对TAC反应的影响。TAC后5周，129 B6 F1小鼠的心脏重量增加最大，129和B6129 F1小鼠的心脏重量增加最小。雌性129 B6 F1和B6小鼠相对免受压力超负荷雄性小鼠心脏重量增加的影响。在129只携带B6 Y染色体的consomic小鼠中，对TAC的反应类似于129而不是129 B6 F1小鼠，表明B6 Y染色体不能解释正反交中的差异。我们的研究结果表明，左心室肥厚的易感性比简单的孟德尔遗传更复杂，父母的起源效应强烈影响这些常用的近交系中的LV对TAC的反应。
Barrick CJ, Dong A, Waikel R, Corn D, Yang F, Threadgill DW, Smyth SS. Parent-of-origin effects on cardiac response to pressure overload in mice. Am J Physiol Heart Circ Physiol 297: H1003-H1009, 2009. First published June 26, 2009; doi: 10.1152/ajpheart.00896.2008. Left ventricular (LV) hypertrophy (LVH) is an independent risk factor for cardiovascular mortality and is commonly caused by hypertension. In rodents, transverse aortic constriction (TAC) is a model regularly employed in mechanistic studies of the response of the LV to pressure overload. We previously reported that inbred strains of male mice manifest different cardiac responses to TAC, with C57BL/6J (B6) developing LV dilatation and impaired contractility and 129S1/SvImJ (129) males displaying concentric LVH. In the present study, we investigated sex and parent-of-origin effects on the response to TAC by comparing cardiac function, organ weights, expression of cardiac hypertrophy markers, and histology in female B6 and female 129 mice and in F1 progeny of reciprocal crosses between B6 and 129 mice (B6129F1 and 129B6F1). Five weeks after TAC, heart weight increased to the greatest extent in 129B6F1 mice and the least extent in 129 and B6129F1 mice. Female 129B6F1 and B6 mice were relatively protected from the increase in heart weight that occurs in their male counterparts with pressure overload. The response to TAC in 129 consomic mice bearing the B6 Y chromosome resembled that of 129 rather than 129B6F1 mice, indicating that the B6 Y chromosome does not account for the differences in the reciprocal cross. Our results suggest that susceptibility to LVH is more complex than simple Mendelian inheritance and that parental origin effects strongly impact the LV response to TAC in these commonly used inbred strains.