Smith S N, Steel D M, Middleton P G, Munkonge F M, Geddes D M, Caplen N J, Porteous D J, Dorin J R, Alton E W
Ion Transport Unit, National Heart and Lung Institute, London, United Kingdom.
Am J Physiol. 1995 Feb;268(2 Pt 1):C297-307. doi: 10.1152/ajpcell.1995.268.2.C297.
Two important issues that can be addressed by animal models are disease pathogenesis and the testing of new treatments, including gene therapy. How closely these models mimic the relevant disorder in humans will determine their usefulness. This study examines how closely the characteristic bioelectric features of cystic fibrosis (CF) are reproduced in the airways and intestinal tract of the exon 10 insertional mutant mouse (cf/cf). In agreement with CF subjects these cf/cf mutant mice demonstrate the following: 1) reduced adenosine 3',5'-cyclic monophosphate-related chloride secretion throughout the respiratory and intestinal tracts both in vivo and in vitro, 2) calcium-related chloride secretion that is preserved in the airways but reduced in the intestine, and 3) a more negative nasal potential difference and increased amiloride response compared with wild-type animals, likely to relate to increased sodium absorption. In contrast to humans, sodium absorption is not increased in the small intestine and is reduced in the trachea of the cf/cf mice. We conclude that the majority of the salient electrophysiological features of CF required for studies of pathogenesis or testing of new treatments are present in these cf/cf mice.
动物模型可以解决的两个重要问题是疾病发病机制和新治疗方法（包括基因治疗）的测试。这些模型与人类相关疾病的模拟程度将决定它们的实用性。本研究考察了外显子10插入突变小鼠（cf/cf）的气道和肠道中囊性纤维化（CF）的特征性生物电特征的重现程度。与CF患者一致，这些cf/cf突变小鼠表现出以下几点：1）体内和体外，整个呼吸道和肠道中与3',5'-环磷酸腺苷相关的氯化物分泌减少；2）与钙相关的氯化物分泌在气道中得以保留，但在肠道中减少；3）与野生型动物相比，鼻电位差更负，对氨氯吡咪的反应增强，这可能与钠吸收增加有关。与人类不同的是，cf/cf小鼠的小肠中钠吸收没有增加，气管中钠吸收减少。我们得出结论，这些cf/cf小鼠具备了用于发病机制研究或新治疗方法测试所需的CF的大部分显著电生理特征。
