Effects of ETI therapy on sensory neurons from △F508 mice

Cystic fibrosis (CF) is a lethal pulmonary disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) channel, which is responsible for chloride and bicarbonate transport. Preliminary results from our lab revealed that sensory neurons from DF508 mice had impaired chloride homeostasis. We hypothesized that treatment of cultured sensory neurons with CFTR modulators (ETI) would restore normal chloride levels. To test this hypothesis, we used mice (male and females) carrying the most common CFTR mutation-causing CF, △F508, and wild-type (WT) littermates to study the intracellular chloride levels with the help of the MQAE chloride-sensitive dye. Our findings show that in both males and females, there was a significant difference in the levels of mean MQAE fluorescent between the genotypes, but ETI did not restore chloride homeostasis. Our data suggests that ETI fails to rescue normal sensory neuron function in a mouse model of CF.