Development of a humanized CF mouse model
(2021) 44th European Cystic Fibrosis Society conference — Location: Digital version
Files
No attached file found for this publication.
Details
- Authors
Mottais, Angélique 
- et. al.
- Abstract
- Animal models are widely used for the study of the pathophysiology of human diseases and the efficacy of new therapies. In the context of cystic fibrosis (CF), several animal (mouse, pig or ferret) models have been developed. However, they show little or no severe respiratory phenotype typically associated with the high morbidity and mortality of the human disease. Based on the observation that the F508del mutation of CFTR leads to a more severe CF phenotype for the human CFTR (hCFTR) than the murine CFTR (mCFTR), this project aims at developing a CF mouse model expressing the hCFTR gene. To obtain the model of interest, two murine lines were generated and then crossed: 1) a line deleted for the mCftr (generated using CRISPR/Cas9) and 2) a line over-expressing the hCFTR (generated by additional transgenesis). Subsequently, the mice obtained were genotyped and characterized. For this purpose, analyses of the overall phenotype (weight curve and height), of the expression of the hCFTR and mCftr genes, of the chloride channel function by measuring nasal potential difference, of the lung phenotype (inflammatory response and bronchopulmonary anatomopathological study) were carried out. Our first observations (reduced growth, dental enamel defect, disorders of the transepithelial transport of chloride through the respiratory epithelium) suggest that hCFTR mice generated present a characteristic CF phenotype with similarities to those pre-established mouse models. These observations require confirmation in a larger number of animals. Moreover, it will also be necessary to refine the phenotypic characterization by further targeting the respiratory function, for example by assessing the inflammatory response not only under naïve conditions but also following induction by well-established bacterial components. The model will hopefully allow a better understanding of the genotype/phenotype differences between the hCFTR and the mCFTR.
- Affiliations
Citations
Mottais, A., & et al. (2021). Development of a humanized CF mouse model. 44th European Cystic Fibrosis Society conference, Digital version. https://hdl.handle.net/2078.5/29494