Thursday, May 11, 2017

Cystic Fibrosis

Cystic Fibrosis (CF) is an inherited autosomal recessive disease resulting from mutations in the CF Transmembrane conductance Regulator (CFTR) gene. CF patients progressively develop a pronounced respiratory phenotype, as the absence of CFTR function in the lung is associated with the thickening of secretions as well as the inability to properly excrete or clear them. This leads to bacteria accumulation and eventually bronchiectasis, allergic bronchopulmonary aspergillosis, and even respiratory failure.


The identification of the CFTR gene in the late 1980s propelled CF research1.  CFTR was identified as a chloride channel and knockout mice were generated, but the early phenotyping studies lacked the sensitivity required to quantify respiratory changes in these mice. It wasn’t until the detailed respiratory mechanics of the flexiVent that the first respiratory CFTR phenotype was reported2.  Various preclinical models of CF are now available3-5 to study the pulmonary manifestations of the CF disease and respiratory mechanics remain an important study outcome in that field.

There is also mounting evidence that CFTR plays a direct role in the airway smooth muscle6. Measuring the reactivity of isolated tracheal rings or strips ex vivo, in tissue baths, allows for a functional assessment in absence of external influences.  This approach was taken to study the effect of CFTR function on human airway smooth muscle and to confirm its role in bronchorelaxation6.



The emka & SCIREQ team will be attending the American Thoracic Society’s 2017 conference in Washington, DC! Come visit our booth #1731 and speak with our experienced team about our solutions for preclinical pediatric research.

1Identification of the cystic fibrosis gene: chromosome walking and jumping – Rommens et al. Science 245: 1059, 1989.
2 The “Goldilocks Effect” in Cystic Fibrosis: Identification of a lung phenotype in cftr knockout and heterozygous mouse – Cohen et al. BMC Genetics., 5: 21, 2004.
3Air trapping and airflow obstruction in newborn cystic fibrosis piglets – Adams et al. Am J Respir Crit Care Med 188: 1434, 2013.
4Lung phenotype of juvenile and adult cystic fibrosis transmembrane conductance regulator knockout ferrets – Sun et al. Am J Respir Cell Mol Biol 50: 502, 2014.
5Early pulmonary disease manifestations in cystic fibrosis mice – Darrah et al. Journal of Cystic Fibrosis 15: 736, 2016.
6Bronchorelaxation of the human bronchi by CFTR activators – Norez et al. ‎Pulm Pharmacol Ther 27: 38, 2014.

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