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Transgenic Ferret Models Define Pulmonary Ionocyte Diversity and Function by Feng Yuan; Grace N. Gasser; Evan Lemire; Daniel T. Montoro; Karthik Jagadeesh; Yan Zhang; Yifan Duan; Vitaly Ievlev; Kristen L. Wells; Pavana G. Rotti; Weam Shahin; Michael Winter; Bradley H. Rosen; Idil Evans; Qian Cai; Miao Yu; Susan A. Walsh; Michael R. Acevedo; Darpan N. Pandya; Vamsidhar Akurathi; David W. Dick; Thaddeus J. Wadas; Nam Soo Joo; Jeffrey J. Wine; Susan Birket; Courtney M. Fernandez; Hui Min Leung; Guillermo J. Tearney; Alan S. Verkman; Peter M. Haggie; Kathleen Scott; Douglas Bartels; David K. Meyerholz; Steven M. Rowe; Xiaoming Liu; Ziying Yan; Adam L. Haber; Xingshen Sun; John F. Engelhardt is a Physics and Astronomy article available to read on EtoBox.

## Abstract Speciation leads to adaptive changes in organ cellular physiology and creates challenges for studying rare cell-type functions that diverge between humans and mice. Rare cystic fibrosis transmembrane conductance regulator (CFTR)-rich pulmonary ionocytes exist throughout the cartilaginous airways of humans^1,2^, but limited presence and divergent biology in the proximal trachea of mice has prevented the use of traditional transgenic models to elucidate ionocyte functions in the airway. Here we describe the creation and use of conditional genetic ferret models to dissect pulmonary ionocyte biology and function by enabling ionocyte lineage tracing (__FOXI1__-Cre^ERT2^::ROSA-TG), ionocyte ablation (__FOXI1__-KO) and ionocyte-specific deletion of __CFTR__ (__FOXI1__-Cre^ERT2^::__CFTR__^L/L^). By comparing these models with cystic fibrosis ferrets^3,4^, we demonstrate that ionocytes control airway surface liquid absorption, secretion, pH and mucus viscosity—leading to reduced airway surface liquid volume and impaired mucociliary clearance in cystic fibrosis, __FOXI1__-KO and __FOXI1__-Cre^ERT2^::__CFTR__^L/L^ ferrets. These processes are regulated by CFTR-dependent ionocyte t

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Author
Feng Yuan; Grace N. Gasser; Evan Lemire; Daniel T. Montoro; Karthik Jagadeesh; Yan Zhang; Yifan Duan; Vitaly Ievlev; Kristen L. Wells; Pavana G. Rotti; Weam Shahin; Michael Winter; Bradley H. Rosen; Idil Evans; Qian Cai; Miao Yu; Susan A. Walsh; Michael R. Acevedo; Darpan N. Pandya; Vamsidhar Akurathi; David W. Dick; Thaddeus J. Wadas; Nam Soo Joo; Jeffrey J. Wine; Susan Birket; Courtney M. Fernandez; Hui Min Leung; Guillermo J. Tearney; Alan S. Verkman; Peter M. Haggie; Kathleen Scott; Douglas Bartels; David K. Meyerholz; Steven M. Rowe; Xiaoming Liu; Ziying Yan; Adam L. Haber; Xingshen Sun; John F. Engelhardt
Publisher
Springer Science and Business Media LLC
Published
2023
Language
EN
Field
Physics and Astronomy (Physical Sciences)