Abstract
Cystic fibrosis (CF) is an autosomal recessive disease that results from mutations in the CF transmembrane conductance regulator (CFTR) gene. The effect of interventions aimed at correcting the CF electrophysiologic phenotype has been primarily measured using in vitro methods in gastrointestinal and respiratory epithelia. A reliable in vivo assay of CFTR function would be of great value in the investigation of pharmacologic interventions for CF mouse models. We performed the in vivo rectal potential difference (RPD) assay on three different mouse models. We then compared the in vivo data with the results obtained using the in vitro Ussing chamber method. The results from the in vitro method correlated closely with the results acquired using the in vivo method and were reproducible. The data suggest that the in vivo RPD assay is a reliable assay of functional CFTR expression in CF mouse models.
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Abbreviations
- Bl6:
-
Black 6
- CF:
-
cystic fibrosis
- CFTR:
-
cystic fibrosis transmembrane conductance regulator
- CFTR(−/+):
-
heterozygous for wild type CFTR and mutant CFTR
- CFTRinh-172:
-
a specific CFTR channel inhibitor
- DCPD:
-
distal colon potential difference
- ΔF508:
-
deletion of phenylalanine at the 508 position
- ΔPDfsk:
-
mean change in potential difference in response to forskolin
- KBR:
-
Kreb's bicarbonate Ringer's solution
- PD:
-
potential difference
- RPD:
-
rectal potential difference
- TMAO:
-
trimethylamine oxide
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Acknowledgements
We would like to acknowledge Dr. Horst Fischer for his extremely helpful communications during the development of our in vivo rectal potential difference assay. We would also like to acknowledge and thank Jeffrey Wisner for his extraordinary technical support.
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This work was supported by grants from the National Institutes of Health (DK53428, MEE) and the Cystic Fibrosis Foundation (EGAN04G0, MEE.). S.A.W. is supported by a training grant from the National Institutes of Health (T32HD07094).
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Weiner, S., Caputo, C., Bruscia, E. et al. Rectal Potential Difference and the Functional Expression of CFTR in the Gastrointestinal Epithelia in Cystic Fibrosis Mouse Models. Pediatr Res 63, 73–78 (2008). https://doi.org/10.1203/PDR.0b013e31815b4bc6
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DOI: https://doi.org/10.1203/PDR.0b013e31815b4bc6
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