da Cunha Mélanie Faria, Simonin Juliette, Sassi Ali, Freund Romain, Hatton Aurélie, Cottart Charles-Henry, Elganfoud Nadia, Zoubairi Rachid, Dragu Corina, Jais Jean Philippe, Hinzpeter Alexandre, Edelman Aleksander, Sermet-Gaudelus Isabelle
INSERM U 1151, Institut Necker Enfants Malades, Université Paris Sorbonne, Paris, France.
Unité de Biostatistiques, Hôpital Necker Enfants Malades, Assistance Publique Hôpitaux de Paris, Paris, France.
Int J Biochem Cell Biol. 2016 Nov;80:87-97. doi: 10.1016/j.biocel.2016.10.001. Epub 2016 Oct 4.
The nasal epithelium of the mouse closely mimics the bioelectrical phenotype of the human airways. Ion transport across the nasal epithelium induces a nasal transepithelial potential difference. Its measurement by a relatively non-invasive method adapted from humans allows in vivo longitudinal measurements of CFTR-dependent ionic transport in the murine nasal mucosa. This test offers a useful tool to assess CFTR function in preclinical studies for novel therapeutics modulating CFTR activity. Here we extensively review work done to assess transepithelial transport in the murine respiratory epithelium in the basal state and after administration of CFTR modulators. Factors of variability and discriminative threshold between the CF and the WT mice for different readouts are discussed.
小鼠的鼻上皮细胞与人类气道的生物电表型极为相似。离子跨鼻上皮细胞运输会诱导产生鼻跨上皮电位差。通过一种借鉴自人体的相对非侵入性方法对其进行测量,能够对小鼠鼻黏膜中CFTR依赖性离子运输进行体内纵向测量。该测试为评估新型CFTR活性调节剂在临床前研究中的CFTR功能提供了一个有用的工具。在此,我们广泛回顾了为评估基础状态下以及给予CFTR调节剂后小鼠呼吸道上皮细胞的跨上皮运输所开展的工作。还讨论了不同读数情况下CF小鼠和野生型小鼠之间的变异性因素和鉴别阈值。