. 2021 Apr 27;12:662110. doi: 10.3389/fphar.2021.662110

TABLE 1.

Knock-in CF animal models.

Species	Mutation	Editing technology	Insertion	CF phenotype	References
Mouse	F508del	Plasmid	HR	Peritonitis, intestinal obstruction	Colledge et al. (1995)
				Electrophysiological abnormalities in trachea and colon epithelium
				Distention and mucus hyper-accumulation in intestinal glands and colon mRNA expression lower than WT
Mouse	F508del	Plasmid	HR	Growth retardation	van Doorninck et al. (1995)
				Hypertrophy of goblet cells in intestine
				Residual CFTR function in nasal, intestinal and gallbladder epithelium
Mouse	F508del	Plasmid	HR	Growth retardation	Zeiher et al. (1995)
				Peritonitis, intestinal obstruction
				Electrophysiological abnormalities in nasal, intestinal and pancreatic epithelium
				Inflammatory cells in broncho-alveolar lavage
Mouse	G551D	Plasmid	HR	Intestinal obstruction, peritonitis	Delaney et al. (1996)
Mouse	G551D	Plasmid	HR	Electrophysiological abnormalities in nasal, tracheal and intestinal epithelium	Delaney et al. (1996)
Mouse	G480C	Plasmid	HR	Hypertrophy of goblet cells in intestine	Dickinson et al. (2002)
Mouse	G480C	Plasmid	HR	Electrophysiological abnormalities in nasal epithelium	Dickinson et al. (2002)
Mouse	R117H	NR	HR	Growth retardation	van Heeckeren et al. (2004)
Mouse	R117H	NR	HR	Electrophysiological abnormalities in nasal epithelium	van Heeckeren et al. (2004)
Pig	F508del	rAAV	HR	Intestinal obstruction	Rogers et al. (2008), Ostedgaard et al. (2011)
				Liver steatosis
				Pancreatic abnormalities
				CF lung disease: Airway obstruction, host-defense defect
				Residual CFTR function in nasal and pancreatic epithelium
Mouse	G542X	CRISPR/Cas9	HR	Growth retardation	McHugh et al. (2018)
				Intestinal obstruction
				No CFTR activity in airway and intestinal epithelium
Rat	F508del	CRISPR/Cas9	HR	Growth retardation	Dreano et al. (2019)
				Abnormal dentition
				Intestinal obstruction
				Residual CFTR function in airway and colon epithelium
Ferret	G551D	rAAV	HR	Intestinal obstruction mRNA expression reduced in lung and intestine	Sun et al. (2019)
				Protein expression reduced in lung
				Electrophysiological abnormalities in intestinal organoids, jejunum and pancreatic ductal epithelium
				Airway obstruction
				Reproductive tract malformations
Rat	F508del	CRISPR/Cas9	HR	Growth retardation	McCarron et al. (2020)
				Abnormal dentition
				Intestinal obstruction
				Residual CFTR function in nasal epithelium
				Reproductive tract malformations
Rat	G542X	CRISPR/Cas9	HR	Growth retardation	Sharma et al. (2020)
				Abnormal dentition
				Intestinal obstruction
				No CFTR activity in airway and intestinal epithelium mRNA degradation (NMD)

Abbreviations: CRISPR/Cas, Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein; HR, Homologous recombination based on the presence of flanking homology arms; KO, Knock-out; NMD, Nonsense-mediated decay; NPD, Nasal potential difference; WT, Wild-type.