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Correlative LM/TEM Studies are Essential in Evaluating the Effectiveness of Liposome Mediated Delivery of the Cystic Fibrosis Transmembrane Regulator (CFTR) as a Corrective Therapy in a CFTR Knockout Mouse that Develops Lung Disease

Published online by Cambridge University Press:  02 July 2020

C.A. Ackerley
Affiliation:
Divisions of Pathology 555 University Ave., Toronto. Ont., Canada., M5G1X8
A. Tilups
Affiliation:
Divisions of Pathology 555 University Ave., Toronto. Ont., Canada., M5G1X8
C.E. Bear
Affiliation:
Cell Biology, Hospital for Sick Children, 555 University Ave., Toronto. Ont., Canada., M5G1X8
L.E. Becker
Affiliation:
Divisions of Pathology 555 University Ave., Toronto. Ont., Canada., M5G1X8
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Extract

An animal model for Cystic Fibrosis (CF) has been developed to further comprehend the pathogenesis of the disease as well as the development of therapeutic interventions. This is a mouse line from a phenotype of an inbred congenic strain of CFTR-knockout mouse that spontaneously develops lung disease. Pathology of the mice include severe impairment of the mucociliary transport, postbronchiolar over inflation of alveoli and parenchymal interstitial thickening with evidence of fibrosis and inflammatory cell invasion.

Although protein replacement therapy using liposomes containing purified reconstituted functional CFTR has been done on the nasal epithelium of CFTR-knockout mice the strain did not develop lung disease nor were the liposomes applied beyond the nasal cavity. Assessment of the treatments was done by measuring the transepithelial potential difference (PD), immunofluorescent labeling of the CFTR and immunogold labeling of the segments of nasal epithelium which were found to have a correction in their PD readings and CFTR present by immunofluorescence. It was clear after these studies that some form of correlative microscopy technique was needed to be devised in order to improve the efficiency of detection.

Type
Biological Labeling and Correlative Microscopy
Copyright
Copyright © Microscopy Society of America

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