TABLE 2.
Introduction of human CFTR to generate humanized CFTR animal models.
| Species | Background | Mutation | Construction | Insertion | CF phenotype | References |
|---|---|---|---|---|---|---|
| Mouse | Cftr tmUnc null mice | hCFTR cDNA under control of FABP promoter | Plasmid | Random insertion | Gastro-intestinal pathology rescued by gut-specific expression of hCFTR under the FABP promoter | Zhou et al. (1994) |
| Mouse | Cftr tm1Cam null mice | hCFTR full gene + regulatory elements (70 kb of flanking sequence) | YAC | Random insertion | Different function according to the founder | Manson et al. (1997) |
| CFTR function rescued in colon, jejunum and cecum with hCFTR expression under endogenous promoter | ||||||
| Mouse | Cftr tm1Cam null mice | hG542X-CFTR cDNA under control of FAPB promoter | Plasmid | Random insertion | Growth retardation | Du et al. (2002) |
| Intestinal obstruction | ||||||
| Occasional weak cAMP-stimulated current in intestinal epithelium | ||||||
| Mouse | Cftr tmUnc null mice | hCFTR full gene + regulatory elements (40.1 kb | BAC | Random insertion | Abnormal dentition | Gawenis et al. (2019) |
| At 5′; 25 kb at 3′ end of hCFTR gene) | Morphological and functional (nasal and intestinal mucosa) rescue with hCFTR expression under endogenous promoter | |||||
| Rat | WT sprague-dawley rat | hG551D-CFTR cDNA (2–27 exons) under control of endogenous promoter | ZFN and super-exon | HR | Growth retardation | Birket et al. (2020) |
| Abnormal dentition | ||||||
| Intestinal obstruction | ||||||
| ASL depletion, PCL decrease, mucus transport decrease and presence of viscous mucus |
Abbreviations: ASL, airway surface liquid; BAC, Bacterial artificial chromosome; FABP, Fatty acid binding protein; hCFTR, human CFTR; HR, Homologous recombination; KO, Knock-out; PCL, periciliary liquid; YAC, yeast artificial chromosome; WT, wild-type; ZFN, Zinc finger nuclease.