Centro de Estudios Científicos (CECS), Avenida Arturo Prat 514, Valdivia 5110466, Chile.
Exp Physiol. 2010 Jun;95(6):686-98. doi: 10.1113/expphysiol.2009.051102. Epub 2010 Feb 12.
Mice have proven to be powerful models for the study of human physiology and pathophysiology. With the advent of techniques for genomic manipulation, the possibilities for studying inherited diseases in this convenient laboratory mammal are increasing by the day. It has been reported that when knocking out or otherwise modifying genes of interest in mice, the phenotype obtained can vary markedly depending on the genetic background of the animals used in the study. The aim of this work was to study whether the genetic background can influence the characteristics of fluid and electrolyte transepithelial transport in the distal colon of three mouse strains most in use in our and other laboratories. Ussing chamber recordings revealed that the colons of C57Bl/6J, Sv 129 and Black Swiss animals have distinctive responses to the calcium agonists carbachol and histamine that are not explained by the presence of different types of muscarinic and histaminergic receptors in these tissues. We have also found differences in the cAMP-activated, KCNMA1-channel-dependent potassium secretion between the strains. We interpret this to indicate a unique distribution of KCNMA1 channels in lower parts of the crypt of Sv 129 colonic epithelium compared with that of C57Bl/6J and Black Swiss animals. The reported differences should be taken into account when choosing the genetic background of animals to be used for genetic modification.
小鼠已被证明是研究人类生理学和病理生理学的有力模型。随着基因组操作技术的出现，研究这种方便的实验室哺乳动物中遗传性疾病的可能性日益增加。据报道，当在小鼠中敲除或修饰感兴趣的基因时，获得的表型可能因研究中使用的动物的遗传背景而异。本工作的目的是研究遗传背景是否会影响三种在我们和其他实验室中最常用的小鼠品系的远端结肠中液体和电解质跨上皮转运的特性。Ussing 室记录表明，C57Bl/6J、Sv 129 和 Black Swiss 动物的结肠对钙激动剂卡巴胆碱和组胺的反应具有独特的特征，而这些组织中不同类型的毒蕈碱和组氨酸能受体的存在并不能解释这些特征。我们还发现了这些品系之间 cAMP 激活的、KCNMA1 通道依赖性钾分泌的差异。我们将这解释为表明与 C57Bl/6J 和 Black Swiss 动物相比，Sv 129 结肠上皮隐窝下部的 KCNMA1 通道分布独特。在选择用于基因修饰的动物的遗传背景时，应考虑到报告的差异。
