Influence of genetic background on ex vivo and in vivo cardiac function in several commonly used inbred mouse strains
Influence of genetic background on ex vivo and in vivo cardiac function in several commonly used inbred mouse strains
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DOI：
10.1152/physiolgenomics.00071.2010
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发表时间：
2010-09-29
影响因子：
4.6
通讯作者：
Metzger, Joseph M.
中科院分区：
文献类型：
--
作者：
Barnabei, Matthew S.;Palpant, Nathan J.;Metzger, Joseph M.
Barnabei MS，Palpant NJ，Metzger JM.遗传背景对几种常用近交系小鼠离体和体内心脏功能的影响。Physiol Genomics 42A：103-113，2010.首次发表于2010年7月13日; doi：10.1152/physiolgenomics.00071.2010.-近交系小鼠在生物医学研究中发挥着关键作用。近交系内的遗传同质性和它们对遗传操作的一般顺从性使它们成为解剖单个基因的生理功能的理想资源。然而，近亲繁殖使近交系小鼠如此有用，也导致它们之间的遗传差异。这种遗传差异往往是无法解释的，但可能是一个混杂因素时，比较研究，利用不同的近交系。在这里，我们将C57 BL/6 J小鼠的心脏功能与其他七种常用的近交系小鼠品系进行了比较：FVB/NJ、DBA/2 J、C3 H/HeJ、BALB/cJ、129 X1/SvJ、C57 BL/10 SnJ和129 S1/SvImJ。用于比较心脏功能的测定是离体分离的Langendorff心脏制备和使用电导微测压法的体内实时血流动力学分析。我们报告了C57 BL/6 J和其他常用的近交系之间的心脏功能的显着应变依赖性差异。C57 BL/6 J在离体缺血后比大多数近交系保持更好的心脏功能，特别是与129 S1/SvImJ、129 X1/SvJ和C57 BL/10 SnJ品系相比。然而，在体内急性缺氧期间，129 X1/SvJ和129 S1/SvImJ保持相对正常的心脏功能，而C57 BL/6 J动物显示出显著的心脏失代偿。此外，与其他菌株的作用相比，C3 H/HeJ对艾司洛尔输注的反应显示出快速和显著的心脏失代偿。这些发现证明了近交系之间的遗传差异对心脏功能的复杂影响。这些结果可能有助于为基因消融或转基因研究的分析提供信息，并进一步证明特定的数量性状可能有助于发现与心脏健康和疾病相关的遗传修饰剂。
Barnabei MS, Palpant NJ, Metzger JM. Influence of genetic background on ex vivo and in vivo cardiac function in several commonly used inbred mouse strains. Physiol Genomics 42A: 103-113, 2010. First published July 13, 2010; doi:10.1152/physiolgenomics.00071.2010.-Inbred mouse strains play a critical role in biomedical research. Genetic homogeneity within inbred strains and their general amenability to genetic manipulation have made them an ideal resource for dissecting the physiological function(s) of individual genes. However, the inbreeding that makes inbred mice so useful also results in genetic divergence between them. This genetic divergence is often unaccounted for but may be a confounding factor when comparing studies that have utilized distinct inbred strains. Here, we compared the cardiac function of C57BL/6J mice to seven other commonly used inbred mouse strains: FVB/NJ, DBA/2J, C3H/HeJ, BALB/cJ, 129X1/SvJ, C57BL/10SnJ, and 129S1/SvImJ. The assays used to compare cardiac function were the ex vivo isolated Langendorff heart preparation and in vivo real-time hemodynamic analysis using conductance micromanometry. We report significant strain-dependent differences in cardiac function between C57BL/6J and other commonly used inbred strains. C57BL/6J maintained better cardiac function than most inbred strains after ex vivo ischemia, particularly compared with 129S1/SvImJ, 129X1/SvJ, and C57BL/10SnJ strains. However, during in vivo acute hypoxia 129X1/SvJ and 129S1/SvImJ maintained relatively normal cardiac function, whereas C57BL/6J animals showed dramatic cardiac decompensation. Additionally, C3H/HeJ showed rapid and marked cardiac decompensation in response to esmolol infusion compared with effects of other strains. These findings demonstrate the complex effects of genetic divergence between inbred strains on cardiac function. These results may help inform analysis of gene ablation or transgenic studies and further demonstrate specific quantitative traits that could be useful in discovery of genetic modifiers relevant to cardiac health and disease.