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Comparative Biology of Cystic Fibrosis Animal Models

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Cystic Fibrosis

Part of the book series: Methods in Molecular Biology ((MIMB,volume 742))

Abstract

Animal models of human diseases are critical for dissecting mechanisms of pathophysiology and developing therapies. In the context of cystic fibrosis (CF), mouse models have been the dominant species by which to study CF disease processes in vivo for the past two decades. Although much has been learned through these CF mouse models, limitations in the ability of this species to recapitulate spontaneous lung disease and several other organ abnormalities seen in CF humans have created a need for additional species on which to study CF. To this end, pig and ferret CF models have been generated by somatic cell nuclear transfer and are currently being characterized. These new larger animal models have phenotypes that appear to closely resemble human CF disease seen in newborns, and efforts to characterize their adult phenotypes are ongoing. This chapter will review current knowledge about comparative lung cell biology and cystic fibrosis transmembrane conductance regulator (CFTR) biology among mice, pigs, and ferrets that has implications for CF disease modeling in these species. We will focus on methods used to compare the biology and function of CFTR between these species and their relevance to phenotypes seen in the animal models. These cross-species comparisons and the development of both the pig and the ferret CF models may help elucidate pathophysiologic mechanisms of CF lung disease and lead to new therapeutic approaches.

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Acknowledgments

This work was supported by grants from the NHLBI (RC1HL099516), NIDDK (P30DK054759, R37DK047967), NHLBI (HL091842) and the Cystic Fibrosis Foundation (ENGELH08XX0), as well as by the Roy J. Carver Chair in molecular medicine. We also gratefully acknowledge Drs Christine Blaumueller and Monali Sawai for editorial contributions.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA

    John T. Fisher, Yulong Zhang & John F. Engelhardt

  2. Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, USA

    John F. Engelhardt

  3. Center for Gene Therapy, Carver College of Medicine, University of Iowa, Iowa City, IA, USA

    John F. Engelhardt

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  1. John T. Fisher
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  2. Yulong Zhang
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  3. John F. Engelhardt
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Correspondence to John F. Engelhardt .

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Editors and Affiliations

  1. Faculty of Sciences, Centre for Biodiversity & Functional, University of Lisboa, Campo Grande, Lisboa, 1749-016, Portugal

    Margarida D. Amaral

  2. , Department of Physiology, University of Regensburg, Universitätsstr. 31, Regensburg, 93053, Germany

    Karl Kunzelmann

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Fisher, J.T., Zhang, Y., Engelhardt, J.F. (2011). Comparative Biology of Cystic Fibrosis Animal Models. In: Amaral, M., Kunzelmann, K. (eds) Cystic Fibrosis. Methods in Molecular Biology, vol 742. Humana Press. https://doi.org/10.1007/978-1-61779-120-8_19

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