Table 1.
CF organ phenotypes in mammalian animal models
| Model species | Spontaneous lung infections | Lung mucus defects | Impaired growth | Intestinal pathology | Exocrine pancreas destruction | Endocrine pancreas dysfunction^ | CFRD | Hepaticpathology | Gallbladder pathology | CFTR modulator responsive genotypes | References |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Human | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Many | |
| Pig | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | G551D, F508del | 54,130–133 |
| Sheep | Unknown | Glands | Unknown | Yes | Yes | Unknown | Unknown | Yes | Yes | F508del | 53,134 |
| Ferret | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | G551D, F508del | 42,51,55–57,60–62,135,136 |
| Rabbit | No | No | Yes | Yes | No | Unknown | No | No | No | F508del† | 137,138 |
| Rat | No | Glands | Yes | Yes | No | Unknown | No | No | NA | Humanized G551D* | 139–143 |
| Mouse | No | No | Yes | Yes | No | Mild to none | No | No | No | Humanized G551D, F508del* | 33,46–48,144–147 |
NA, not applicable since the organ does not exist in this species; glands, limited to submucosal gland mucus accumulation and/or obstruction; unknown, not yet studied; mild to none, some studies show certain abnormalities following β-cell injury with streptozotocin.
Endocrine pancreatic dysfunction means alterations to glucose metabolism and insulin secretion.
F508del rabbit model has been generated, but it remains unknown if the rabbit mutant CFTR is responsive to CFTR modulators.
Mouse and rat CFTR mutants are not responsive to CFTR modulators, thus humanized models were generated that either randomly insert the human CFTR mutant gene locus into the mouse genome or insert a CFTR mutant cDNA into the rat Ctfr locus.