Cystic fibrosis animal models

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), a chloride (CF) channel characterised by chloride permeability and secretion, and also by the regulation of other epithelial ion channels (Eidelman et al, 2001). Mutations in the CFTR gene lead to an impaired or absent Cl conductance in the epithelial apical membrane, which leads to defective Cl secretion and absorption across the epithelium. Genistein (Illek et al, 1995 Weinreich et al, 1997) and other flavonoids (Illek and Fisher, 1998) have been shown, in different animal and tissue models, to activate wild-type CFTR and CFTR mutants by (Eidelman et al, 2001 Roomans, 2001 Suaud et al, 2002) ... 

The routes of delivery of rAAV in animal models have been largely based upon the specific needs dictated by the disease process to be treated. For example, rAAV-cystic fibrosis transmembrane conductance regulator (CFTR) vectors that have been developed for treatment of cystic fibrosis (CF) were tested in New Zealand white rabbits and in rhesus macaques by the endobronchial route (Flotte et al., 1993 Afione et al., 1996 Conrad et al., 1996). In each instance aliquots of vector were instilled directly into the lumen of a bronchus through a fiberoptic bronchoscope. Vector DNA transfer and mRNA expression were detectable (albeit at low levels) for more than 6 months in each instance, without any indication of inflammation or any other toxicity. Studies in rhesus monkeys also indicated that the likelihood of rescue of rAAV by concomitant wild-type AAV and adenovirus infection was low. These studies... 

The possible functional role of decreased expression of IL-10 in pulmonary inflammation and bacterial clearance in cystic fibrosis has also been investigated in animal models. As might be surmised from the known properties of IL-10, these studies have collectively suggested that the reduced levels of IL-10 seen in adults with cystic fibrosis are associated with a potentiation of pulmonary inflammation and with an impairment of the clearance of P. aeruginosa. In a... 

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